Novel imaging agents for detecting neurological dysfunction

ABSTRACT

Disclosed here in are compounds and methods of diagnosing Alzheimer&#39;s Disease or a predisposition thereto in a mammal, the method comprising administering to the mammal a diagnostically effective amount of a radiolabeled compound, wherein the compound is selected from the group consisting of radiolabeled flavones, coumarins, carbazoles, quinolinones, chromenones, imidazoles and triazoles derivatives, allowing the compound to distribute into the brain tissue, and imaging the brain tissue, wherein an increase in binding of the compound to the brain tissue compared to a normal control level of binding indicates that the mammal is suffering from or is at risk of developing Alzheimer&#39;s Disease.

RELATED APPLICATIONS

The present application is based on and claims the priority of U.S.provisional application No. 60/066,101, filed Feb. 14, 2008, which isincorporated herein by reference.

Alzheimer's disease (AD), a leading cause of dementia, develops in onepercent of the population between the ages 65 and 69, and increasing to40-50% in those 95 years and older. AD patients exhibit telltaleclinical symptoms that include cognitive impairment and deficits inmemory function. In these patients, heavy senile plaque burden found inthe cerebral cortex, verified by post mortem histopathologicalexamination, confirms the presence of AD. The mature senile plaquesconsist of intracellular neurofibrillary tangles (NFT) derived fromfilaments of hyperphosphorylated tau proteins, and extracellularβ-amyloid peptides derived from enzymatic processing of amyloidprecursor protein. Interestingly, despite the development and presenceof senile plaques in elderly persons with normal cognitive function, theseverity of NFT and senile plaque deposition purportedly correlates witha loss of cognitive function and neuronal circuitry deterioration.

Despite Alzheimer's disease being the fourth leading cause of death inthe United States, pharmaceutical intervention has yet to commercializea curative therapy. Instead, clinicians currently prescribecholinesterase inhibitors to cognitively impaired patients.Rivastigmine, a therapeutic treatment for both AD and Parkinson diseasepatients, inhibits both acetylcholinesterase and butyrylcholinesterase,preventing the breakdown of acetyl- and butyrylcholine. Galantamine, anaturally derived acetylcholinesterase inhibitor, increases nicotiniccholinergic receptors to release acetylcholine into the brain. As afinal example, the acetylcholinesterase inhibitor Aricept slowsprogression of AD in patients by inhibiting acetylcholinesterase andthus increasing cortical acetylcholine. In a recent clinical trial,Aricept's effectiveness slowed AD progression in patients but thetherapeutic effects disappeared after 36 months. The effect of treatingAD patients with a therapeutic combination of both Aricept and memantinecaused an increased cognitive function in those AD patients relative tothose who just received only Aricept. Despite the usefulness ofcholinesterase inhibitors, the current array of AD therapeutics can onlydelay full-onset AD by approximately two to three years, after whichthey are therapeutically ineffective in inhibiting cognitive decline. Ithas been reported that delaying AD onset by five years is sufficient toreduce the number of AD cases in half and, given the currentshortcomings of cholinesterase inhibitors, further research efforts arerequired to meet that goal.

Neurological imaging of AD has seen the emergence of imaging tracersthat appear to confirm the presence of AD based on plaque and fibrilmediated tracer uptake and, subsequently, are currently undergoingextensive clinical examination. Many of these tracers contain chemotypesthat derive from fluorescent dyes (Table 1). For example, increaseduptake and binding of the napthylaniline derivative ¹⁸F-FDDNP in livingbrains correlates well with the presence of AD when compared tocognitively functional normals of similar age. [Liu, J., et al.,High-Yield, Automated Radiosynthesis of 2-(1-{6-[(2-[¹⁸F]Fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malonitrile ([¹⁸F]FDDNP) Ready for Animal or Human Administration. Molecular Imaging andBiology, 2007. 9: p. 6-16.] A competing compound, ¹¹C-PIB, showsenhanced uptake in frontotemporal and hippocampal brain regions in ADpatients when compared to healthy normals.

There are several issues, however, that question the validity of imagingsenile plaques and tangles. First, the current array of AD imagingagents can only confirm the well-established manifestation of AD andthis late stage diagnosis offers little defense against further diseaseprogression past 36 months. Secondly, the detection of senile plaquesand tangles may not correlate to development of the early stages of AD.Recent data suggests that the amyloid cascade model [Hardy, J. and D.Selkoe, The Amyloid Hypothesis of Alzheimer's Disease: Progress andProblems on the Road to Therapeutics. Science, 2002. 297: p. 353-356]does not accurately depict the primary factors leading to cognitivedecline in AD patients and that other contributing factors, such asneuorotoxic soluble oligomers and aggregates may play a contributoryrole in neurodegeneration. [Talaga, P., Inhibitors of beta-amyloidaggregation: still an issue of structure and function? Drug DiscoveryToday: Therapeutic Strategies, 2004. 1: p. 7-12]. To date, FDDNP and PIBare not known to bind to neurotoxic soluble oligomers and aggregates andthus are not expected to differentiate accurately between the earlystages of AD from the advanced stages of AD in patients.

As summarized from a recent discussion group on Dec. 5, 2006,(Biochemical Pharmacology Discussion Group, cosponsored by the AmericanChemical Society's New York section), researchers are now focusing onmethods that target AD precursors by blocking either β-amyloid protein(BAP) production or by controlling mutant tau protein formation.Clearly, this focused research effort aims to control the formation ofAD precursors that potentially lead to AD and this new strategy mightdelay full-onset AD more effectively that current therapeutics. Inparallel, neurological imaging must mirror the therapeutic trend byidentifying AD precursors in a duel effort to compliment both ADtherapeutic development and, in addition, identify presymptomaticat-risk AD patients.

A number of medical diagnostic procedures, including PET and SPECTutilize radiolabeled compounds, are well known in the art. PET and SPECTare very sensitive techniques and require small quantities ofradiolabeled compounds, called tracers. The labeled compounds aretransported, accumulated and converted in vivo in exactly the same wayas the corresponding non-radioactively compound. Tracers, or probes, canbe radiolabeled with a radionuclide useful for PET imaging, such as ¹¹C,¹³N, ¹⁵O, ¹⁸F, ⁶⁴Cu and ¹²⁴I, or with a radionuclide useful for SPECTimaging, such as ⁹⁹Tc, ⁷⁷Br, ⁶¹Cu, ¹⁵³Gd, ¹²³I, ¹²⁵I, ¹³¹I and ³²P.

PET creates images based on the distribution of molecular imagingtracers carrying positron-emitting isotopes in the tissue of thepatient. The PET method has the potential to detect malfunction on acellular level in the investigated tissues or organs. PET has been usedin clinical oncology, such as for the imaging of tumors and metastases,and has been used for diagnosis of certain brain diseases, as well asmapping brain and heart function. Similarly, SPECT can be used tocomplement any gamma imaging study, where a true 3D representation canbe helpful, for example, imaging tumor, infection (leukocyte), thyroidor bones.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is directed to compounds having the structuralFormula I where the radicals have the meanings given above.

“Halogen” or “halo” means F, Cl, Br and I.

“Alkyl” means a saturated monovalent hydrocarbon radical having straightor branched moieties. Examples of alkyl groups include, but are notlimited to, methyl, ethyl, n-propyl, isopropyl and t-butyl.

“Alkenyl” means an alkyl moieties having at least one carbon-carbondouble bond wherein alkyl is as defined above. Examples of alkenylinclude, but are not limited to, ethenyl and propenyl.

“Alkynyl” means alkyl moieties having at least one carbon-carbon triplebond wherein alkyl is as defined above. Examples of alkynyl groupsinclude, but are not limited to, ethynyl and 2-propynyl.

“Alkylene” or “alkenylenyl” means a saturated, divalent hydrocarbonradicals i.e., generally present as a bridging or linking group betweentwo other groups, having straight or branched moieties. Examples ofalkylene groups include —CH₂— (methylene); —CH₂CH₂— (ethylene);—CH₂CH₂CH₂— (propylene), —CH(CH₃)CH₂— (isopropylene) etc.

“Amino” means a nitrogen moiety having two further substituents where ahydrogen or carbon atom is attached to the nitrogen. For example,representative amino groups include —NH₂, —NHCH₃, —N(CH₃)₂,—NHC₂₋₃-alkyl, —N(C₂₋₃-alkyl)₂ and the like. Unless indicated otherwise,the compounds of the invention containing amino moieties may includeprotected derivatives thereof. Suitable protecting groups for aminomoieties include acetyl, tert-butoxycarbonyl, benzyloxycarbonyl and thelike.

“Aryl” means an organic radical derived from an aromatic hydrocarbon byremoval of one hydrogen, such as phenyl, naphthyl, indenyl, indanyl andfluorenyl. “Aryl” encompasses fused ring groups wherein at least onering is aromatic.

“Cycloalkyl” means non-aromatic saturated cyclic alkyl moietiesconsisting of one or more rings, wherein said rings (if more than one)share at least one carbon atom, wherein alkyl is as defined above.Examples of cycloalkyl include, but are not limited to, cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclo-[3.1.0]-hexyl,bicyclo-[2.2.1]-hept-1-yl, norbornyl, spiro[4.5]decyl, spiro[4.4]nonyl,spiro[4.3]octyl, spiro[4.2]heptyl and adamantanyl.

“HaloC₁₋₆alkyl” means a C₁₋₆alkyl group that is substituted with atleast one halogen atom on a carbon atom of the alkyl group.Non-exclusive, representative examples of such haloC₁₋₆alkyl includeF—CH₂—, F—CH₂CH₂—, F—CH₂CH₂CH₂—, CHF₂—, CHF₂CH₂—, CHF₂CH₂CH₂—, Br—CH₂—,Br—CH₂CH₂—, Br—CH₂CH₂CH₂—, CHBr₂—, CHBr₂CH₂—, CHBr₂CH₂CH₂— and the like.

“Heterocyclic” or “heterocycloalkyl” means a non-aromatic cyclic groupsconsisting of one or more rings, wherein the rings (if more than one)share one or two atoms and each ring contains up to four heteroatoms(i.e. from zero to four heteroatoms, provided that at least one ringcontains at least one heteroatom). The heterocyclic groups of thisinvention can also include ring systems substituted with one or more O,S(O)_(0.2), and/or N—R¹⁰ as heteroatoms, wherein R¹⁰ is as definedherein, and wherein the subscript “0-2” of S(O)₀₋₂ represents an integerof 0, 1 or 2. Thus, S(O)₂ represents the group consisting of S, S(═O),and S(O)₂. Examples of non-aromatic heterocyclic groups are aziridinyl,azetidinyl, pyrrolidinyl, piperidinyl, azepinyl, piperazinyl,1,2,3,6-tetrahydropyridinyl, oxiranyl, oxetanyl, tetrahydropyranyl,tetrahydrothienyl, tetrahydropyranyl, tetrahydrothiopyranyl, morpholino,thiomorpholino, thioxanyl, pyrrolinyl, indolinyl, 2H-pyranyl,4H-pyranyl, dioxanyl, 1,3-dioxolanyl, pyrazolinyl, dihydropyranyl,dihydrothienyl, dihydropyranyl, pyrazolidinyl, imidazolinyl,imidazolidinyl, 3-azabicyclo[3.1.0]hexanyl, 3-azabicyclo[4.1.0]heptanyl,quinolizinyl, quinuclidinyl, 1,4-dioxaspiro[4.5]decyl,1,4-dioxaspiro[4.4]nonyl, 1,4-dioxaspiro[4.3]octyl and1,4-dioxaspiro[4.2]heptyl.

“Heteroaryl” means an aromatic group containing one or more heteroatoms(O, S, or N), preferably from one to four heteroatoms. A heteroaryl maybe a monocyclic or a polycyclic group. Examples of heteroaryl groups arepyridinyl, pyridazinyl, imidazolyl, pyrimidinyl, pyrazolyl, triazolyl,pyrazinyl, quinolyl, isoquinolyl, 1,2,3,4-tetrahydroguinolyl,tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl,isothiazolyl, pyrrolyl, indolyl, benzimidazolyl, benzofuranyl,indazolyl, indolizinyl, phthalazinyl, triazinyl, 1,3,5-triazinyl,isoindolyl, purinyl, oxadiazolyl, thiadiazolyl, furazanyl,benzofurazanyl, benzothiophenyl, benzotriazolyl, benzothiazolyl,benzoxazolyl, quinazolinyl, quinoxalinyl, naphthyridinyl,dihydroquinolyl, tetrahydroquinolyl, dihydroisoquinolyl,tetrahydroisoquinolyl, benzofuryl, furopyridinyl, pyrolopyrimidinyl andazaindolyl. In certain aspects of the present application, theheteroaryl is a 4-substituted-1H-1,2-3-triazol-1-yl.

As used herein, where a divalent group, such as a linker for example, isrepresented by a structure -A-B-, as shown below, it is intended to alsorepresent a group that may be attached in both possible permutations, asnoted in the two structures below.

may also be

For example, when a divalent group such as the group “—N(R¹⁰)C(O)—” isprovided, for example, the group is intended to also include both thedivalent group —N(R¹⁰)C(O)— and also the divalent group —C(O)N(R¹⁰)—.

The substituents or the groups C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkyl,heteroaryl, heteroaryloxy etc. . . . of the variables R¹, R², R³, R⁴,R⁵, R⁶, R⁷, R⁸, R⁹ and R¹⁰ are also optionally further substituted bysubstituents selected from the group consisting of amino, halo, cyano,nitro, hydroxyl, —SH, —SC₁₋₆alkyl, —C(O)NH₂, —C(S)NH₂, halo C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkyl, C₆₋₁₄aryland heteroaryl.

For example, in certain aspect of the present application, theheteroaryl substituent is a 4-substituted-1H-1,2-3-triazol-1-yl. In theradiolabeled compounds of the present application, a radionuclide may beattached to an aryl group of the compound of Formulae I to VI, as in a2-¹⁸F-carbazole derivative such as the compound represented as:

or a 2-(¹⁸F-fluoroethyl)-'carbazole, 2-(¹⁸F-fluoromethyl)-'carbazole, a¹¹C-methoxy-group, for example, and/or the radionuclide may be attachedto any one or more of the variables R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹and R¹⁰ by way of a ¹⁸F-fluoroethyl-group, a ¹⁸F-fluoromethyl-group, a¹¹C-methoxy-group,4-[(¹⁸F-fluoroethyl)-1H-1,2-3-triazol-1-yl]ethoxy-group,4-[(¹⁸F-fluoroethyl)-1H-1,2,3-triazol-1-yl]-propyloxy-group, a ¹²³I, a¹²⁴I, a ¹²⁵I or a ¹³¹I group, and the like. Unless otherwise noted, acompound represented as being substituted by an atom, such as thegeneric representation by the atom fluorine in F—CH₂CH₂—('carbazole) orF—CH₂CH₂O-('carbazole), for example, is intended to cover both thenaturally occurring element ¹⁹F (fluorine-19) as well as the ¹⁸F(fluorine-18) isotope(s) of the element itself.

The term “optionally substituted” or “substituted” refers to thespecific substituents or groups wherein one to four hydrogen atoms inthe group may be replaced by one to four substituents, for example,independently selected from the substituents amino, halo, cyano, nitro,hydroxyl, —SH, —SC₁₋₆alkyl, —C(O)NH₂, —C(S)NH₂, haloC₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkyl, C₆₋₁₄aryland heteroaryl, or as specifically disclosed herein. In addition, thesubstituents may also include alkyl, aryl, alkylene-aryl, hydroxy,alkoxy, aryloxy, perhaloalkoxy, heterocyclyl, azido, amino, guanidino,amidino, halo, alkylthio, oxo, acylalkyl, carboxy esters, carboxyl,carboxamido, acyloxy, aminoalkyl, alkylaminoaryl, alkylaminoalkyl,alkoxyaryl, arylamino, phosphono, sulfonyl, carboxamidoaryl,hydroxyalkyl, haloalkyl, alkoxyalkyl and perhaloalkyl. In addition, theterm “optionally substituted” or “substituted” in reference to thevariables R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹ and R¹⁰, includes groupssubstituted by one to four substituents, as identified above, thatfurther comprise a positron or gamma emitter. Such positron emittersinclude, but are not limited to, ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I,¹³¹I and ⁷⁷Br.

The term “radiolabeled compound” as used herein refers to compoundshaving an atom or group that may provide a radiolabel or may beconverted to a radiolabel, such as from a non-radioactive atom to aradionuclide that is active, such as for example, ¹¹C, ¹³N, ¹⁵O, ¹⁸F,¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br. In addition, for the purpose of thepresent application, such “radiolabeled compound” may also refer to anatom or a group, that comprises a non-active nuclide, such as a halogen,such as ¹⁹F for example, wherein the compound may be used andadministered in a therapeutically effective amount.

Compounds of the Formula Ito Formula VI may have optical centers andtherefore may occur in different enantiomeric and diastereomericconfigurations. The present invention includes all enantiomers,diastereomers, and other stereoisomers of such compounds of the FormulaIto Formula VI, as well as racemic compounds and racemic mixtures andother mixtures of stereoisomers thereof. Pharmaceutically acceptablesalts of the compounds of Formula Ito Formula VI include the acidaddition and base salts thereof. Suitable acid addition salts are formedfrom acids which form non-toxic salts. Examples include, but are notlimited to, the acetate, adipate, aspartate, benzoate, besylate,bicarbonate/carbonate, bisulphate/sulphate, borate, citrate, formate,fumarate, gluconate, glucuronate, hydrochloride/chloride,hydrobromide/bromide, hydroiodide/iodide, lactate, malate, maleate,malonate, mesylate, methylsulphate, naphthylate, oxalate, palmitate,phosphate/hydrogen phosphate/dihydrogen phosphate, pyroglutamate,salicylate, stearate, succinate, sulfonate, tartrate, tosylate andtrifluoroacetate salts. Suitable base salts are formed from bases whichform non-toxic salts. Examples include, but are not limited to, thealuminum, arginine, benzathine, calcium, choline, diethylamine,diolamine, glycine, lysine, magnesium, potassium, sodium, tromethamineand zinc salts. Hemisalts of acids and bases may also be formed, forexample, hemisulphate and hemicalcium salts. For a review on suitablesalts, see Handbook of Pharmaceutical Salts: Properties, Selection, andUse by Stahl and Wermuth (Wiley-VCH, 2002). Pharmaceutically acceptablesalts of compounds of Formula Ito Formula VI may be prepared by one ormore of three methods: (i) by reacting the compound of Formula ItoFormula VI with the desired acid or base; (ii) by removing an acid- orbase-labile protecting group from a suitable precursor of the compoundof Formula Ito Formula VI; or (iii) by converting one salt of thecompound of Formula Ito Formula VI to another salt by the reaction withan appropriate acid or base or by means of a suitable ion exchangecolumn.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 shows Biacore binding assay results.

FIG. 2 shows representative scaffolds for compounds found to bindoligomer, polymers and/or fibrils.

FIG. 3A shows UV HPLC analysis of AD-CB-001P-WZ-01019 synthesis ofAD-CB-002P-WZ01031.

FIG. 3B shows Gamma HPLC analysis of AD-CB-001P-WZ-01019 synthesis ofAD-CB-002P-WZ01031.

FIG. 4 shows immunostaining of brain sections with thioflavin T,thioflavin T with tracer and no thioflavin T.

FIG. 5 shows immunostaining of brain sections with FDDNP, FDDNP withtracer and no FDDNP.

FIG. 6 shows coronal slices of a white rat brain using 1 min framing.After 2 minutes, the tracer concentration reaches a maximum level in thebrain and is completely washed out after 7 minutes.

FIG. 7 shows amyloid autoradiography staining (ex vivo) of an ADpatient's brain with [18F]-CB-001 shows good amyloid binding andlittle/no white matter binding.

FIG. 8 shows [18F]-CB001 competition studies on AD Brain slicesdemonstrate reversible plaque binding and competition with PiB, andlittle/no white matter binding.

FIG. 9 shows the optimal staining and wash protocol indicating tracerspecific.

FIG. 10 shows [18F]-CB003 clearly distinguishes between Alzheimer's andnormal brains.

FIG. 11 shows concentration-dependent blocking of [18F]-PiB tissuebinding with PiB and CB003.

FIG. 12 shows surface plasmon resonance assay results of CB003 bindingto Aβ42 insoluble aggregates.

FIG. 13 shows surface plasmon resonance assay results of CB003 bindingto Aβ42 soluble aggregates.

FIG. 14 shows surface plasmon resonance assay results of PiB binding toAβ42 insoluble aggregates.

FIG. 15 shows surface plasmon resonance assay results of PiB binding toAβ42 soluble aggregates.

FIG. 16 shows surface plasmon resonance assay results of CB004 bindingto Aβ42 insoluble aggregates.

FIG. 17 shows surface plasmon resonance assay results of CB004 bindingto Aβ42 soluble aggregates.

FIG. 18A shows MicroPET imaging, 2 min p.i., with [18F]-CB-001 in Appand WT mice demonstrates very good brain uptake.

FIG. 18B shows MicroPET imaging, 20-30 min p.i., with [18F]-CB-001 inApp and WT mice demonstrates very good brain uptake.

FIG. 19 shows MicroPET imaging, 10 min, with [18F]-CB003 in WT and Appmice.

FIG. 20 left panel shows MicroPET imaging analysis with [18F]-CB003 inindividual WT and App mice. Right panel shows combined MicroPET imaginganalysis with [18F]-CB003 in WT and App mice.

FIG. 21 shows percent increase of brain/muscle (B/M) ratio for MicroPETimaging analysis with [18F]-CB003 in WT and App mice.

FIG. 22 shows clearance of [18F]PiB in WT and App mice brain.

FIG. 23 shows clearance of [18F]-CB003 in WT and App mice brainindicates that brain clearance of [18F]-CB003 is much faster than with[18F]PiB.

SUMMARY OF THE INVENTION

In one embodiment, there is provided a radiolabeled compound of theFormula Ito Formula VI:

wherein:

For Formula I:

A is N or CR¹; B is N or CR²; J is N or CR³; K is N or CR⁴; L is N orCR⁵; M is N or CR⁶; P is N or CR⁷; and Q is N or CR⁸, provided that nomore than two of A, B, J, K, L, M, P and Q can be N;

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—;

R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or areeach independently selected from the group consisting of amino, halo,cyano, nitro, hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; or at least one ofR¹ and R², R² and R³, R³ and R⁴, R⁵ and R⁶, R⁶ and R⁷, or R⁷ and R⁸together with the carbon atoms to which they are attached to, form asubstituted or unsubstituted aromatic or non-aromatic carbocyclic orheterocyclic ring;

provided that at least any two of R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ arehydrogens;

R⁹ is hydrogen or is selected from the group consisting of halo,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, halo-(CH₂CH₂)₁₋₆—;halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— andhalo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—;

each R¹⁰ is independently H or C₁₋₆alkyl;

provided that the compound of Formula I is not a compound selected fromthe group consisting of 2-fluoroethyl6-fluoro-4-methoxy-9H-pyrido[3,4-b]indole-3-carboxylate, 2-fluoropropyl6-fluoro-4-methoxy-9H-pyrido[3,4-b]indole-3-carboxylate,9H-pyrido[3,4-b]indole-3-carboxylate,9H-pyrido[3,4-b]indole-3-thiocarboxylate,9H-pyrido[3,4-b]indole-3-carboxamide,9H-pyrido[3,4-b]indole-3-carbimidate, β-carboline-3-carboxylate,β-carboline-3-thiocarboxylate, β-carboline-3-carboxamide,β-carboline-3-carbimidate;(S)-4-(3-(3-(2′-18F]-fluoroethylamino)-2-hydroxypropoxy)-carbazol, R, S,SS and SR-1′-[18F]-fluorocarazolol (FCAR) and [11C]-carazolol (CAR),(S)-(+4-(2-hydroxy-3-(1′-[18]fluoroisopropyl)-aminopropoxy)carbazole,7-(2-fluoroethoxy)-1-methyl-9H-β-carboline,7-(2-fluoropropoxy)-1-methyl-9H— β-carboline,7-[2-(2-fluoroethoxy)ethoxy]-1-methyl-9H-β-carboline,7-{2-[2-(2-fluoroethoxy)ethoxy]ethoxy}-1-methyl-9H— β-carboline andcarbazolyl-(4)-oxypropanolamine and their derivatives;

wherein the radiolabel comprises a radionuclide selected from the groupconsisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br;

and pharmaceutically acceptable salts thereof;

For Formula II:

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—;

R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or areeach independently selected from the group consisting of amino, halo,cyano, nitro, hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; or at least one ofR¹ and R², R² and R³, R³ and R⁴, R⁵ and R⁶, R⁶ and R⁷, or R⁷ and R⁸together with the carbon atoms to which they are attached to, form asubstituted or unsubstituted aromatic or non-aromatic carbocyclic orheterocyclic ring;

provided that at least any two of R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ arehydrogens;

R⁹ is hydrogen or is selected from the group consisting of halo,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, halo-(CH₂CH₂)₁₋₆—;halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— andhalo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—;

each R¹⁰ is independently H or C₁₋₆alkyl;

wherein the radiolabel comprises a radionuclide selected from the groupconsisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br.

and pharmaceutically acceptable salts thereof;

For Formula III:

Y and Y′ are each independently a bond or are each independentlyselected from the group consisting of amino, halo, cyano, nitro,hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, haloC₁₋₆alkyl, perhaloC₁₋₆alkyl,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy andheteroaryloxy when R¹¹ and R¹² are absent;

R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or are eachindependently selected from the group consisting of amino, halo, cyano,nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; or at least one ofR⁵ and R⁶, R⁶ and R⁷ or R⁷ and R⁸ together with the carbon atoms towhich they are attached to, form a substituted or unsubstituted aromaticor non-aromatic carbocyclic or heterocyclic ring;

provided that at least one of R⁵, R⁶, R⁷ and R⁸ is a hydrogen;

each R¹⁰ is independently H or C₁₋₆alkyl;

R¹¹ and R¹² are each independently absent, a hydrogen or are eachindependently selected from the group consisting of halo, C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl,heteroaryl, halo-(CH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— and halo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—;

wherein the radiolabel comprises a radionuclide selected from the groupconsisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br.

and pharmaceutically acceptable salts thereof;

For Formula IV:

W is O or —N—X—R⁹;

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—;

Y and Y′ are each independently a bond or are each independentlyselected from the group consisting of amino, halo, cyano, nitro,hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl,heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃ alkyl (OCH₂CH₂)₁₋₆O—,halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—,C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy,C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy and heteroaryloxy when R¹¹ and R¹² areabsent; or Y is

and R¹² is absent;

R¹, R², R³ and R⁴ are each independently hydrogen or are eachindependently selected from the group consisting of amino, halo, cyano,nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃ alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; or at least one ofR⁵ and R⁶, R⁶ and R⁷ or R⁷ and R⁸ together with the carbon atoms towhich they are attached to, form a substituted or unsubstituted aromaticor non-aromatic carbocyclic or heterocyclic ring;

provided that at least one of R¹, R², R³ and R⁴ is a hydrogen;

R⁵, R⁶, R⁷, R⁸ and R^(o) are each independently hydrogen or are eachindependently selected from the group consisting of amino, halo, cyano,nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—;

R⁹ is hydrogen or is selected from the group consisting of halo,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, halo-(CH₂CH₂)₁₋₆—;halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— andhalo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—;

each R¹⁰ is independently H or C₁₋₆alkyl;

R¹¹ and R¹² are each independently absent, a hydrogen or are eachindependently selected from the group consisting of halo, C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl,heteroaryl, halo-(CH₂CH₂)₁₋₆—; halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— and halo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—;

wherein the radiolabel comprises a radionuclide selected from the groupconsisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br.

and pharmaceutically acceptable salts thereof;

For Formula V:

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—;

R⁵ and R⁶ are each independently hydrogen or are each independentlyselected from the group consisting of amino, halo, cyano, nitro,hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₂₋₆alkyl, perhaloC₁₋₆alkyl,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄-alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; or R⁵ and R⁶together with the carbon atoms to which they are attached to, form asubstituted or unsubstituted aromatic or non-aromatic carbocyclic orheterocyclic ring;

R⁹ is hydrogen or is selected from the group consisting of halo,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, halo-(CH₂CH₂)₁₋₆—;halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— andhalo-CH₂CH₂—(OCH₂CH₂)₁₋₆(O)—;

each R¹⁰ is independently H or C₁₋₆alkyl;

wherein the radiolabel comprises a radionuclide selected from the groupconsisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br;

and pharmaceutically acceptable salts thereof;

For Formula VI:

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—;

Y is a bond or is selected from the group consisting of amino, halo,cyano, nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy andheteroaryloxy;

R⁵ and R⁶ are each independently hydrogen or are each independentlyselected from the group consisting of amino, halo, cyano, nitro,hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, haloC₁₋₆alkyl, perhaloC₁₋₆alkyl,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀-arylC(O)O—; or R⁵ and R⁶together with the carbon atoms to which they are attached to, form asubstituted or unsubstituted aromatic or non-aromatic carbocyclic orheterocyclic ring;

R⁹ is hydrogen or is selected from the group consisting of halo,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,heteroaryl, halo-(CH₂CH₂)₁₋₆—; halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— and halo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—;

each R¹⁰ is independently H or C₁₋₆alkyl;

R¹¹ is a hydrogen or is selected from the group consisting of halo,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀-arylC₁₋₄alkyl, heteroaryl, halo-(CH₂CH₂)₁₋₆—;halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— andhalo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—;

provided that at least one of R¹ to R¹² comprises a radiolabel, asdefined herein;

wherein the radiolabel comprises a radionuclide selected from the groupconsisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br;

and pharmaceutically acceptable salts thereof.

In one variation of the above compound:

For Formula I:

A is N or CR¹; B is N or CR²; J is N or CR³; K is N or CR⁴; L is N orCR⁵; M is N or CR⁶; P is N; and Q is N or CR⁸;

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O— and —C(S)O—; and

R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or areeach independently selected from the group consisting of amino, halo,cyano, nitro, hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂, haloC₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀-arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; or at least one ofR¹ and R², R² and R³, R³ and R⁴, R⁵ and R⁶, R⁶ and R⁷, or R⁷ and R⁸together with the carbon atoms to which they are attached to, form asubstituted or unsubstituted aromatic or non-aromatic carbocyclic orheterocyclic ring;

For Formula II:

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)— and —C(S)O—; and

R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or areeach independently selected from the group consisting of amino, halo,cyano, nitro, hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂, haloC₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloallyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₀aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalicylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; or at least one ofR¹ and R², R² and R³, R³ and R⁴, R⁵ and R⁶, R⁶ and R⁷, or R⁷ and R⁸together with the carbon atoms to which they are attached to, form asubstituted or unsubstituted aromatic or non-aromatic carbocyclic orheterocyclic ring;

For Formula III:

Y and Y′ are each independently selected from the group consisting ofamino, halo, cyano, nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂,halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₀aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—, C₃₋₆cycloalkoxy,C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy,C₆₋₁₀arylC₁₋₄alkoxy and heteroaryloxy when R¹¹ and R¹² are absent;

R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or are eachindependently selected from the group consisting of amino, halo, cyano,nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, haloC₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₂₋₅alkoxy, halo-C₂₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₂₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; or at least one ofR¹ and R², R² and R³, R³ and R⁴, R⁵ and R⁶, R⁶ and R⁷, or R⁷ and R⁸together with the carbon atoms to which they are attached to, form asubstituted or unsubstituted aromatic or non-aromatic carbocyclic orheterocyclic ring;

For Formula IV:

W is O or —N—X—R⁹;

R¹, R², R³ and R⁴ are each independently hydrogen or are eachindependently selected from the group consisting of amino, halo, cyano,nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; or at least one ofR¹ and R², R² and R³ or R³ and R⁴ together with the carbon atoms towhich they are attached to, form a substituted or unsubstituted aromaticor non-aromatic carbocyclic or heterocyclic ring;

For Formula V:

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—;

R⁵ and R⁶ are each independently hydrogen or are each independentlyselected from the group consisting of amino, halo, cyano, nitro,hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; and

R⁹ is hydrogen or is selected from the group consisting of halo,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, halo-(CH₂CH₂)₁₋₆—;halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— andhalo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—;

For Formula VI:

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—;

Y is a bond or is selected from the group consisting of amino, halo,cyano, nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, haloC₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy andheteroaryloxy;

R⁵ and R⁶ are each independently hydrogen or are each independentlyselected from the group consisting of amino, halo, cyano, nitro,hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—;

R⁹ is hydrogen or is selected from the group consisting of halo,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, halo-(CH₂CH₂)₁₋₆—;halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— andhalo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—; and

R¹¹ is absent, a hydrogen or is selected from the group consisting ofhalo, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, halo-(CH₂CH₂)₁₋₆—;halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— andhalo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—;

wherein the radiolabel comprises a radionuclide selected from the groupconsisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br;

and pharmaceutically acceptable salts thereof.

In another variation of the above compound:

For Formula I:

A is N or CR¹; B is N or CR²; J is N or CR³; K is N or CR⁴; L is N orCR⁵; M is N or CR⁶; P is N or CR⁷; and Q is N or CR⁸, provided that nomore than two of A, B, J, K, L, M, P and Q can be N;

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—; and

R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or areeach independently selected from the group consisting of amino, halo,cyano, nitro, hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O— and C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—;

For Formula II:

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—; and

R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or areeach independently selected from the group consisting of amino, halo,cyano, nitro, hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂, haloC₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,heteroarylC₂₋₅alkoxy, C₆₋₁₀aryl, C₆₋₁₀-arylC₁₋₄alkyl, heteroaryl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O— and C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—;

For Formula III:

Y and Y′ are each independently a bond or are each independentlyselected from the group consisting of amino, halo, cyano, nitro,hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, haloC₁₋₆alkyl, perhaloC₁₋₆alkyl,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₀aryloxy, C₆₋₁₀arylC₁₋₄alkoxy andheteroaryloxy when R¹¹ and R¹² are absent; and

R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or are eachindependently selected from the group consisting of amino, halo, cyano,nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O— and C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—;

For Formula IV:

W is O or —N—X—R⁹;

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—;

Y and Y′ are each independently a bond or are each independentlyselected from the group consisting of amino, halo, cyano, nitro,hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₆alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy andheteroaryloxy when R¹¹ and R¹² are absent; and

R¹, R², R³ and R⁴ are each independently hydrogen or are eachindependently selected from the group consisting of amino, halo, cyano,nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O— and C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—;

For Formula V:

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—; and

R⁵ and R⁶ are each independently hydrogen or are each independentlyselected from the group consisting of amino, halo, cyano, nitro,hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O— and C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—;

For Formula VI:

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—;

Y is a bond or is selected from the group consisting of amino, halo,cyano, nitro, hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂, haloC₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy andheteroaryloxy when R¹¹ is absent; and

R⁵ and R⁶ are each independently hydrogen or are each independentlyselected from the group consisting of amino, halo, cyano, nitro,hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O— and C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—;

wherein the radiolabel comprises a radionuclide selected from the groupconsisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br;

and pharmaceutically acceptable salts thereof.

In another variation of the above compound:

For Formula I:

A is N or CR¹; B is N or CR²; J is N or CR³; K is N or CR⁴; L is N orCR⁵; M is N or CR⁶; P is N or CR⁷; and Q is N or CR⁸, provided that nomore than two of A, B, J, K, L, M, P and Q can be N;

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—; and

R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or areeach independently selected from the group consisting ofhalo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-and halo-C₁₋₅alkylNR¹⁰C(O)—;

For Formula II:

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—; and

R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or areeach independently selected from the group consisting ofhalo-C₂₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O—, halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)- and halo-C₁₋₅alkylNR¹⁰C(O)—;

For Formula III:

Y and Y′ are each independently a bond or are each independentlyselected from the group consisting of amino, halo, cyano, nitro,hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, haloC₁₋₆alkyl, perhaloC₁₋₆alkyl,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy andheteroaryloxy when R¹¹ and R¹² are absent; and

R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or are eachindependently selected from the group consisting of halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—, FCH₂CH₂—(OCH₂CH₂)₁₋₆O—,haloC₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-and halo-C₁₋₅alkylNR¹⁰C(O)—;

For Formula IV:

W is O or —N—X—R⁹;

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰) and —N(R¹⁰)S(O)₂—;

Y and Y′ are each independently a bond or are each independentlyselected from the group consisting of amino, halo, cyano, nitro,hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₂₋₆alkyl, perhaloC₁₋₆alkyl,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy andheteroaryloxy when R¹¹ and R¹² are absent; and

R¹, R², R³ and R⁴ are each independently hydrogen or are eachindependently selected from the group consisting of halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-and halo-C₁₋₅alkylNR¹⁰C(O)—;

For Formula V:

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—; and

R⁵ and R⁶ are each independently hydrogen or are each independentlyselected from the group consisting of halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-and halo-C₁₋₅alkylNR¹⁰C(O)—;

For Formula VI:

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—;

Y is a bond or is selected from the group consisting of amino, halo,cyano, nitro, hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy andheteroaryloxy when R¹¹ is absent; and

R⁵ and R⁶ are each independently hydrogen or are each independentlyselected from the group consisting of halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O—,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-and halo-C₁₋₅alkylNR¹⁰C(O)—;

wherein the radiolabel comprises a radionuclide selected from the groupconsisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br;

and pharmaceutically acceptable salts thereof.

In one variation of the above compound:

For Formula I:

A is N or CR¹; B is N or CR²; J is N or CR³; K is N or CR⁴; L is N orCR⁵; M is N or CR⁶; P is N or CR⁷; and Q is N or CR⁸, provided that nomore than two of A, B, J, K, L, M, P and Q can be N;

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰) and —N(R¹⁰)S(O)₂—; and

R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or areeach independently selected from the group consisting ofC₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy,C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄ alkoxy, heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—,(C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—;

For Formula II:

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—; and

R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or areeach independently selected from the group consisting ofC₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy,C₆₋₁₄aryloxy, C₆₋₁₀arylC alkoxy, heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—,(C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—;

For Formula III:

Y and Y′ are each independently a bond or are each independentlyselected from the group consisting of amino, halo, cyano, nitro,hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, haloC₁₋₆alkyl, perhaloC₁₋₆alkyl,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₂₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀-arylC₁₋₄alkoxy andheteroaryloxy when R¹¹ and R¹² are absent; and

R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or are eachindependently selected from the group consisting of C₃₋₆cycloalkoxy,C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy,C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy, C₁₋₅alkylNR¹⁰C(O) —,(C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—;

For Formula IV:

W is O or —N—X—R⁹;

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—;

Y and Y′ are each independently a bond or are each independentlyselected from the group consisting of amino, halo, cyano, nitro,hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₂₋₆alkyl, perhaloC₁₋₆alkyl,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy andheteroaryloxy when R¹¹ and R¹² are absent; and

R¹, R², R³ and R⁴ are each independently hydrogen or are eachindependently selected from the group consisting of C₃₋₆cycloalkoxy,C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy,C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—,(C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀-arylC(O)— and C₆₋₁₀-arylC(O)O—;

For Formula V:

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—; and

R⁵ and R⁶ are each independently hydrogen or are each independentlyselected from the group consisting of C₃₋₆cycloalkoxy,C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy,C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—,(C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—;

For Formula VI:

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—;

Y is a bond or is selected from the group consisting of amino, halo,cyano, nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₂₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy andheteroaryloxy when R¹¹ is absent; and

R⁵ and R⁶ are each independently hydrogen or are each independentlyselected from the group consisting of C₃₋₆cycloalkoxy,C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy,C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—,(C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀-arylC(O)O—;

wherein the radiolabel comprises a radionuclide selected from the groupconsisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br;

and pharmaceutically acceptable salts thereof.

In another variation of the above compound:

For Formula I and Formula II:

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—;

R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or areeach independently selected from the group consisting of amino, halo,cyano, nitro, hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; or at least one ofR¹ and R², R² and R³, R³ and R⁴, R⁵ and R⁶, R⁶ and R⁷, or R⁷ and R⁸together with the carbon atoms to which they are attached to, form asubstituted or unsubstituted aromatic or non-aromatic carbocyclic orheterocyclic ring;

provided that at least any two of R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ arehydrogens;

R⁹ is hydrogen or is selected from the group consisting of halo,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, halo(CH₂CH₂)₁₋₆—;haloCH₂CH₂—(OCH₂CH₂)₁₋₆—, haloCH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— andhaloCH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—; and

each R¹⁰ is independently H or C₁₋₆alkyl;

For Formula III:

Y and Y′ are each independently a bond or are each independentlyselected from the group consisting of amino, halo, cyano, nitro,hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, haloC₁₋₆alkyl, perhaloC₁₋₆alkyl,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy andheteroaryloxy when R¹¹ and R¹² are absent; and

R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or are eachindependently selected from the group consisting of amino, halo, cyano,nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,haloC₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, haloC₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; or at least one ofR¹ and R², R² and R³, R³ and R⁴, R⁵ and R⁶, R⁶ and R⁷, or R⁷ and R⁸together with the carbon atoms to which they are attached to, form asubstituted or unsubstituted aromatic or non-aromatic carbocyclic orheterocyclic ring;

provided that at least any two of R⁵, R⁶, R⁷ and R⁸ are hydrogens;

R⁹ is hydrogen or is selected from the group consisting of halo,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, halo(CH₂CH₂)₁₋₆—;halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— andhalo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—; and

each R¹⁰ is independently H or C₁₋₆alkyl;

For Formula IV:

W is O or —N—X—R⁹;

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—;

Y and Y′ are each independently a bond or are each independentlyselected from the group consisting of amino, halo, cyano, nitro,hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy andheteroaryloxy when R¹¹ and R¹² are absent; and

R¹, R², R³ and R⁴ are each independently hydrogen or are eachindependently selected from the group consisting of amino, halo, cyano,nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,haloC₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, haloC₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,haloC₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀-arylC(O)O—; or at least one ofR¹ and R², R² and R³ or R³ and R⁴ together with the carbon atoms towhich they are attached to, form a substituted or unsubstituted aromaticor non-aromatic carbocyclic or heterocyclic ring;

provided that at least any two of R¹, R², R³ and R⁴ are hydrogens;

R⁹ is hydrogen or is selected from the group consisting of halo,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, halo-(CH₂CH₂)₁₋₆—;halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— andhalo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—; and

each R¹⁰ is independently H or C₁₋₆alkyl;

For Formula V:

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—; and

R⁵ and R⁶ are each independently each independently hydrogen or are eachindependently selected from the group consisting of amino, halo, cyano,nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, haloC₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀-arylC(O)— and C₆₋₁₀arylC(O)O—;

R⁹ is hydrogen or is selected from the group consisting of halo,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, halo-(CH₂CH₂)₁₋₆;halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— andhalo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—; and

each R¹⁰ is independently H or C₁₋₆alkyl;

For Formula VI:

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—;

Y is a bond or is selected from the group consisting of amino, halo,cyano, nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, haloC₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₂₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy andheteroaryloxy when R¹¹ is absent; and

R⁵ and R⁶ are each independently each independently hydrogen or are eachindependently selected from the group consisting of amino, halo, cyano,nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—;

R⁹ is hydrogen or is selected from the group consisting of halo,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, halo-(CH₂CH₂)₁₋₆—;halo-CH₂CH₂—(OCH₂CH₂)₁₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— andhalo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—; and

each R¹⁰ is independently H or C₁₋₆alkyl;

wherein the radiolabel comprises a radionuclide selected from the groupconsisting of ¹¹C, ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br;

and pharmaceutically acceptable salts thereof.

In another variation of the above compound:

For Formula I and Formula II:

R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or areeach independently selected from the group consisting of amino, halo,cyano, nitro, hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂, C₁₋₅alkoxy,H(OCH₂CH₂)₁₋₆O— and C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—;

For Formula III:

R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or are eachindependently selected from the group consisting of amino, halo, cyano,nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—and C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—;

For Formula IV:

R¹, R², R³ and R⁴ are each independently hydrogen or are eachindependently selected from the group consisting of amino, halo, cyano,nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—and C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—.

For Formula V and Formula VI:

R⁵ and R⁶ are each independently hydrogen or are each independentlyselected from the group consisting of amino, halo, cyano, nitro,hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O— andC₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,

wherein the radiolabel comprises a radionuclide selected from the groupconsisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br;

and pharmaceutically acceptable salts thereof.

In a particular variation of each of the above compounds, thehalo-moiety of the group selected from halo-C₁₋₆alkyl, halo-C₂₋₅alkoxy,halo-C₂₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O—,halo-(CH₂CH₂)₁₋₆—; halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—,halo-C₂₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₂₋₆alkylOC(O)CH(C₁₋₅alkyl)-and haloC₁₋₅alkylNR¹⁰C(O)— is selected from the group consisting offluoro, iodo and bromo. In another variation of the above:

For Formula I and Formula II:

R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or areeach independently selected from the group consisting ofhalo-C₂₋₅alkoxy, haloC₁₋₆alkyl, perhaloC₁₋₆alkyl,halo-C₂₋₃alkyl(OCH₂CH₂)₁₋₆O—, F—CH₂CH₂O—, F—CH₂CH₂—(OCH₂CH₂)₁₋₆O—,haloC₂₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, haloC₂₋₆alkylOC(O)CH(C₁₋₅alkyl)-and haloC₂₋₅alkylNR¹⁰C(O)—;

For Formula III:

R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or are eachindependently selected from the group consisting of halo-C₁₋₅alkoxy,haloC₁₋₆alkyl, perhaloC₁₋₆alkyl, halo-C₂₋₃alkyl(OCH₂CH₂)₁₋₆O—,F—CH₂CH₂O—, F—CH₂CH₂—(OCH₂CH₂)₁₋₆O—,haloC₂₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, haloC₂₋₆alkylOC(O)CH(C₁₋₅alkyl)-and haloC₂₋₅alkylNR¹⁰C(O)—;

For Formula IV:

R¹, R², R³ and R⁴ are each independently hydrogen or are eachindependently selected from the group consisting of halo-C₁₋₅alkoxy,haloC₁₋₆alkyl, perhaloC₁₋₆alkyl, halo-C₂₋₃alkyl(OCH₂CH₂)₁₋₆O—,F—CH₂CH₂O—, F—CH₂CH₂—(OCH₂CH₂)₁₋₆O—,haloC₂₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, haloC₂₋₆alkylOC(O)CH(C₁₋₅alkyl)-and haloC₂₋₅alkylNR¹⁰C(O)—;

For Formula V and Formula VI:

R⁵ and R⁶ are each independently hydrogen or are each independentlyselected from the group consisting of halo-C₁₋₅alkoxy, haloC₁₋₆alkyl,perhaloC₁₋₆alkyl, halo-C₂₋₃alkyl(OCH₂CH₂)₁₋₆O—, F—CH₂CH₂O—,F—CH₂CH₂—(OCH₂CH₂)₁₋₆O—, haloC₂₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-,haloC₂₋₆alkylOC(O)CH(C₁₋₅alkyl)- and haloC₂₋₅alkylNR¹⁰C(O)—;

wherein the radiolabel comprises a radionuclide selected from the groupconsisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br;

and pharmaceutically acceptable salts thereof.

In yet another variation:

For Formula I and Formula II:

R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or areeach independently selected from the group consisting of C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, heteroaryl C₂₋₅alkoxy,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₃₋₆cycloalkoxy,C₃₋₁₂cycloalkylC₁₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy,heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—, C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— andC₆₋₁₀arylC(O)O—;

For Formula III:

R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or are eachindependently selected from the group consisting of C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, heteroarylC₂₋₅alkoxy,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₃₋₆cycloalkoxy,C₃₋₁₂cycloalkylC₁₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy,heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—, C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— andC₆₋₁₀arylC(O)O—;

For Formula IV:

R¹, R², R³ and R⁴ are each independently hydrogen or are eachindependently selected from the group consisting of C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, heteroaryl C₂₋₅alkoxy,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₃₋₆cycloalkoxy,C₃₋₁₂cycloalkylC₁₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy,heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—, C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— andC₆₋₁₀arylC(O)O—;

For Formula V and Formula VI:

R⁵ and R⁶ are each independently hydrogen or are each independentlyselected from the group consisting of C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, heteroarylC₂₋₅alkoxy, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₃₋₆cycloalkoxy,C₃₋₁₂cycloalicylC₁₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄ alkoxy,heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—, C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— andC₆₋₁₀arylC(O)O—;

wherein the radiolabel comprises a radionuclide selected from the groupconsisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br;

and pharmaceutically acceptable salts thereof.

In yet another variation:

For Formula I and Formula II:

R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen orselected from the group consisting of F—C₁₋₆alkyl, F—C₁₋₅alkoxy,F—C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, F—CH₂CH₂O—, F—CH₂CH₂—(OCH₂CH₂)₁₋₆O—,4-(F—C₁₋₆alkyl)-1H-1,2,3-triazol-1-yl-(C₂₋₅alkoxy),F—C₂₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, F—C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)- andF—C₁₋₅alkylNR¹⁰C(O)—;

For Formula III:

R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or selected from thegroup consisting of F—C₁₋₆alkyl, F—C₁₋₅alkoxy,F—C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, F—CH₂CH₂O—, F—CH₂CH₂—(OCH₂CH₂)₁₋₆O—,4-(F—C₁₋₆alkyl)-1H-1,2,3-triazol-1-yl-(C₂₋₅alkoxy),F—C₂₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, F—C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)- andF—C₁₋₅alkylNR¹⁰C(O)—;

For Formula IV:

R¹, R², R³ and R⁴ are each independently hydrogen or selected from thegroup consisting of F—C₁₋₆alkyl, F—C₁₋₅alkoxy,F—C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, F—CH₂CH₂O—, F—CH₂CH₂—(OCH₂CH₂)₁₋₆O—,4-(F—C₁₋₆alkyl)-1H-1,2,3-triazol-1-yl-(C₂₋₅alkoxy),F—C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, F—C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)- andF—C₁₋₅alkylNR¹⁰C(O)—;

For Formula V and Formula VI:

R⁵ and R⁶ are each independently hydrogen or selected from the groupconsisting of F—C₁₋₆alkyl, F—C₁₋₅alkoxy, F—C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,F—CH₂CH₂O—, F—CH₂CH₂—(OCH₂CH₂)₁₋₆O—,4-(F—C₁₋₆alkyl)-1H-1,2,3-triazol-1-yl-(C₂₋₅alkoxy),F—C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, F—C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)- andF—C₁₋₅alkylNR¹⁰C(O)—;

wherein the radiolabel comprises a radionuclide selected from the groupconsisting of ¹¹C, ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br;

and pharmaceutically acceptable salts thereof.

In another particular variation of the above:

For Formula I and Formula II:

at least four of R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are hydrogens;

For Formula III:

at least two of R⁵, R⁶, R⁷ and R⁸ are hydrogens;

For Formula IV:

at least two of R¹, R², R³ and R⁴ are hydrogens;

For Formula V and Formula VI:

at least one of R⁵ or R⁶ is a hydrogen;

wherein the radiolabel comprises a radionuclide selected from the groupconsisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br; andpharmaceutically acceptable salts thereof.

In yet another variation of each of the above, the amino group isselected from the group consisting of NH₂—, CH₃NH—, (CH₃)₂N—,C₁₋₃-alkylNH—, F—C₂₋₃-alkylNH—, F—(C₂₋₃-alkylO)₁₋₄-alkyl-NH—,(C₁₋₃-alkyl)₂N—, C₁₋₆alkylNH—, (C₁₋₆alkyl)₂N—, C₃₋₆cycloalkylNH—,(C₃₋₆cycloalkyl)₂N—, C₃₋₁₂cycloalkylC₁₋₅alkylNH—, C₆₋₁₄arylNH—,C₆₋₁₀arylC₁₋₄alkylNH—, heteroarylNH—, C₆₋₁₄aryloxyNH—,C₆₋₁₀-arylC₁₋₄alkoxyNH— and heteroaryloxyNH—. In a particular variationof the Formula I, II, V and VI, X is a bond and R⁹ is hydrogen.

In another aspect of each of the above compound, the compound comprisesat least one radionuclide selected from the group consisting of ¹¹C,¹⁵O, ¹⁸F_(,) ¹²³I, ¹²⁵I, ¹³¹I and ⁷⁷Br.

In another aspect, there is provided a radiolabeled compound wherein thecompound is selected from 2-(2-fluoroethoxy)-9H-carbazole;9-(2-fluoroethyl)-9H-carbazol-2-ol;N-(2-fluoroethyl)-7-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-9H-carbazol-3-amine;7-(2-fluoroethoxy)-N,N-dimethyl-9H-carbazol-2-amine;7-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-N-methyl-9H-carbazol-3-amine;1-(3,6-diamino-9H-carbazol-9-yl)-3-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)propan-1-one;N-(2-fluoroethyl)-2-hydroxy-11H-benzo[a]carbazole-3-carboxamide;2-(6-chloro-9H-carbazol-2-yl)-N-(2-fluoroethyl)propanamide;2-(6-fluoro-9H-carbazol-2-yl)-N,N-dimethylpropanamide;2-methoxy-9H-carbazole; 6-iodo-2-methoxy-9H-carbazole;2-(2-fluoroethoxy)-9H-carbazole; 9-(2-fluoroethyl)-9H-carbazol-2-ol;N-(2-fluoroethyl)-7-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-9H-carbazol-3-amine;7-(2-fluoroethoxy)-N,N-dimethyl-9H-carbazol-2-amine;7424242-fluoroethoxy)ethoxy)ethoxy)-N-methyl-9H-carbazol-3-amine;1-(3,6-diamino-9H-carbazol-9-yl)-3-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)propan-1-one;N-(2-fluoroethyl)-2-hydroxy-11H-benzo[a]carbazole-3-carboxamide;2-(6-chloro-9H-carbazol-2-yl)-N-(2-fluoroethyl)propanamide; and2-(6-fluoro-9H-carbazol-2-yl)-N,N-dimethylpropanamide.

In another embodiment, there is provided a radiolabeled compound of theformula IIa:

wherein:

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂;

R², R³, R⁴, R⁶, R⁷ and R⁸ are each independently hydrogen or are eachindependently selected from the group consisting of amino, halo, cyano,nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—;

provided that at least any two of R², R³, R⁴, R⁶, R⁷ and R⁸ arehydrogens, and at least one of R², R³, R⁴, R⁶, R⁷, R⁸ and R⁹ comprisesthe radiolabel;

R⁹ is hydrogen or is selected from the group consisting of halo,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, halo-(CH₂CH₂)₁₋₆—;halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— andhalo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—;

each R¹⁰ is independently H or C₁₋₆alkyl;

wherein the radiolabel comprises a radionuclide selected from the groupconsisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br; andpharmaceutically acceptable salts thereof.

In one variation of the above, X is a bond or is selected from the groupconsisting of C₁₋₆alkylenyl, —C(O)—, —C(O)O— and —N(R¹⁰)C(O)—;

R², R³, R⁴, R⁶, R⁷ and R⁸ are each independently hydrogen or are eachindependently selected from the group consisting of C₁₋₃alkylNH—, halo,cyano, hydroxyl, —SR¹⁰, —C(O)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloallylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy, C₆₋₁₄aryloxy,C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy, heteroarylC₂₋₅alkoxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; and

R⁹ is hydrogen or is selected from the group consisting of halo,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀aryl C₁₋₄alkyl, heteroaryl, halo-(CH₂CH₂)₁₋₆—;halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— andhalo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—. In another variation of the above, X is abond or is selected from the group consisting of C₁₋₆alkylenyl, —C(O)—,—C(O)O— and —N(R¹⁰)C(O)—;

R², R⁴, R⁶ and R⁸ are each hydrogen;

R³ and R⁷ are each independently selected from the group consisting ofC₁₋₃alkylNH—, (C₁₋₃alkyl)₂N—, (halo-C₁₋₆alkyl)N(C₁₋₃alkyl)-,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆N(C₁₋₃alkyl)-, halo, hydroxyl, halo-C₁₋₆alkyl,C₆₋₁₀-arylC₁₋₄alkyl, 4-(halo-C₁₋₆alkyl)-triazol-1-yl)C₂₋₅alkoxy,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylC(O)—; and

R⁹ is hydrogen or is selected from the group consisting of halo,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,halo-(CH₂CH₂)₁₋₆—; halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— and halo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—.

In another embodiment, there is provided a radiolabeled compound of theformula III:

wherein: Y and Y′ are each independently a bond or are eachindependently selected from the group consisting of amino, halo, cyano,nitro, hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂, haloC₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy andheteroaryloxy when R¹¹ and R¹² are absent;

R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or are eachindependently selected from the group consisting of amino, halo, cyano,nitro, hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; or at least one ofR⁵ and R⁶, R⁶ and R⁷ or R⁷ and R⁸ together with the carbon atoms towhich they are attached to, form a substituted or unsubstituted aromaticor non-aromatic carbocyclic or heterocyclic ring;

provided that at least one of R⁵, R⁶, R⁷ and R⁸ is a hydrogen;

each R¹⁰ is independently H or C₁₋₆alkyl;

R¹¹ and R¹² are each independently absent, a hydrogen or are eachindependently selected from the group consisting of halo, C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl,heteroaryl, halo-(CH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— and halo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—;

provided that at least one of R⁵ to R¹² comprises a radiolabel;

wherein the radiolabel comprises a radionuclide selected from the groupconsisting of ¹¹C, ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br;and pharmaceutically acceptable salts thereof. In one variation of theabove, Y and Y′ are each independently selected from the groupconsisting of amino, halo, hydroxyl, —SR¹—C(O)NH₂, —C(S)NH₂,halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₁₋₅alkoxy,H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O— and halo-CH₂CH₂O— when R¹¹ and R¹² areabsent; and

R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or are eachindependently selected from the group consisting of amino, halo,hydroxyl, —SR¹⁰—C(O)NH₂, haloC₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl,C₃₋₆cycloalkyl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy,H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₂₋₅alkoxy,halo-C₂₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—, C₃₋₆cycloalkoxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₂₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-and halo-C₁₋₅alkylNR¹⁰C(O)—.

In another variation of the above, Y and Y′ are each independently abond or are each independently selected from the group consisting ofamino, halo, hydroxyl, —C(O)NH₂, haloC₁₋₆alkyl, perhaloC₁₋₆alkyl,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC_(i) alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—and halo-CH₂CH₂O— when R¹¹ and R¹² are absent; and

R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or are eachindependently selected from the group consisting of halo-C₁₋₅alkoxy,halo-C₁₋₃ alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—, FCH₂CH₂—(OCH₂CH₂)₁₋₆O—,haloC₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-and halo-C₁₋₅alkylNR¹⁰C(O)—.

In yet another variation of the above, Y and Y′ are each independently abond or are each independently selected from the group consisting ofamino, halo, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, haloC₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-C₂₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—,C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy,C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy and heteroaryloxy when R¹¹ and R¹² areabsent; and

R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or are eachindependently selected from the group consisting of C₃₋₆cycloalkoxy,C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy,C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—,(C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-, C₁₋₅alkylC(O)—, C₁₋₅alkylC(O)O—,C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—.

In another embodiment, there is provided a radiolabeled compound of theformula IV:

wherein:

W is O or —N—X—R⁹;

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—;

Y and Y′ are each independently a bond or are each independentlyselected from the group consisting of amino, halo, cyano, nitro,hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy andheteroaryloxy when R¹¹ and R¹² are absent; or Y is

and R¹² is absent;

R¹, R², R³ and R⁴ are each independently hydrogen or are eachindependently selected from the group consisting of amino, halo, cyano,nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; or at least one ofR⁵ and R⁶, R⁶ and R⁷ or R⁷ and R⁸ together with the carbon atoms towhich they are attached to, form a substituted or unsubstituted aromaticor non-aromatic carbocyclic or heterocyclic ring;

provided that at least one of R¹, R², R³ and R⁴ is a hydrogen;

R⁵, R⁶, R⁷, R⁸ and R^(o) are each independently hydrogen or are eachindependently selected from the group consisting of amino, halo, cyano,nitro, hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀-arylC₁₋₄ alkyl, heteroaryl, C₁₋₅alkoxy,H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—, C₃₋₆cycloalkoxy,C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy,C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—,(C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₅alkylNR¹⁰C(O)—,C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—, C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— andC₆₋₁₀arylC(O)O—;

R⁹ is hydrogen or is selected from the group consisting of halo,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, halo-(CH₂CH₂)₁₋₆—;halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— andhalo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—;

each R¹⁰ is independently H or C₁₋₆alkyl; and

R¹¹ and R¹² are each independently absent, a hydrogen or are eachindependently selected from the group consisting of halo, C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₀aryl, C₆₋₁₀arylC₁₋₄alkyl,heteroaryl, halo-(CH₂CH₂)₁₋₆—; halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— and halo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—;

provided that at least one of R¹¹ to R¹² comprises a radiolabel, asdefined herein;

wherein the radiolabel comprises a radionuclide selected from the groupconsisting of ¹¹C, ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br;and pharmaceutically acceptable salts thereof.

In one variation of the above compound, W is O or —N—X—R⁹;

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—; and

R¹, R², R³ and R⁴ are each independently hydrogen or are eachindependently selected from the group consisting of amino, halo, cyano,nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—.

In one variation of the above compound, W is O or —N—X—R⁹;

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(O)O— and —N(R¹⁰)C(O)—;

Y and Y′ are each independently a bond or are each independentlyselected from the group consisting of amino, halo, cyano, nitro,hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—, C₆₋₁₄aryloxy,C₆₋₁₀-arylC₁₋₄alkoxy and heteroaryloxy when R¹¹ and R¹² are absent; and

R¹, R², R³ and R⁴ are each independently hydrogen or are eachindependently selected from the group consisting of amino, halo,hydroxyl, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, heteroarylC₂₋₅alkoxy, C₁₋₅alkoxy,H(OCH₂CH₂)₁₋₆O— and C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,

In another variation of the above compound, W is O;

Y and Y′ are each independently a bond or are each independentlyselected from the group consisting of amino, halo, hydroxyl, —SR¹⁰,—C(O)NH₂, halo-C₂₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—, C₃₋₆cycloalkoxy,C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy,C₆₋₁₀arylC₁₋₄alkoxy and heteroaryloxy when R¹¹ and R¹² are absent; and

R¹, R², R³ and R⁴ are each independently hydrogen or are eachindependently selected from the group consisting of halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-and halo-C₁₋₅alkylNR¹⁰C(O)—.

In yet another variation of the above compound, W is O;

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(O)O—;

Y and Y′ are each independently a bond or are each independentlyselected from the group consisting of amino, halo, hydroxyl, —C(O)NH₂,—C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O— and halo-CH₂CH₂O— when R¹¹ and R¹² areabsent; and

R¹, R², R³ and R⁴ are each independently hydrogen or are eachindependently selected from the group consisting of amino, halo,hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—and halo-CH₂CH₂O—; or at least one of R¹ and R², R² and R³ or R³ and R⁴together with the carbon atoms to which they are attached to, form asubstituted or unsubstituted aromatic or non-aromatic carbocyclic orheterocyclic ring;

provided that at least any two of R¹, R², R³ and R⁴ are hydrogens;

R⁹ is hydrogen or is selected from the group consisting of halo,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, halo-(CH₂CH₂)₁₋₆—;halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— andhalo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—; and each R¹⁰ is independently H orC₁₋₆alkyl.

In another embodiment, there is provided a radiolabel compound of theformula VI:

wherein:

X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—;

Y is a bond or is selected from the group consisting of amino, halo,cyano, nitro, hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy andheteroaryloxy;

R⁵ and R⁶ are each independently hydrogen or are each independentlyselected from the group consisting of amino, halo, cyano, nitro,hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, haloC₁₋₆alkyl, perhaloC₁₋₆alkyl,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂ cycloalkyl C₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; or R⁵ and R⁶together with the carbon atoms to which they are attached to, form asubstituted or unsubstituted aromatic or non-aromatic carbocyclic orheterocyclic ring;

R⁹ is hydrogen or is selected from the group consisting of halo,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, halo-(CH₂CH₂)₁₋₆—;halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— andhalo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—;

each R¹⁰ is independently H or C₁₋₆alkyl;

R¹¹ is a hydrogen or is selected from the group consisting of halo,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, halo-(CH₂CH₂)₁₋₆—;halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— andhalo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—;

provided that at least one of R¹ to R¹¹ comprises a radiolabel, asdefined herein;

wherein the radiolabel comprises a radionuclide selected from the groupconsisting of ¹¹C, ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br;and pharmaceutically acceptable salts thereof.

In one variation of the above compound, X is a bond or is selected fromthe group consisting of C₁₋₆alkylenyl, —C(O)—, —C(O)O—;

Y is a bond or is selected from the group consisting of amino, halo,—SR¹⁰—C(O)NH₂, —C(S)NH₂, haloC₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀-arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—and halo-CH₂CH₂O—;

R⁵ and R⁶ are each independently hydrogen or are each independentlyselected from the group consisting of amino, halo, hydroxyl,—SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl,heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—,C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy,C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—,(C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₅alkylNR¹⁰C(O)—,C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—, C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— andC₆₋₁₀arylC(O)O—;

R⁹ is hydrogen or is selected from the group consisting of halo,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀-arylC₁₋₄alkyl, halo-(CH₂CH₂)₁₋₆—; halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— and halo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—; and

R¹¹ is absent, a hydrogen or is selected from the group consisting ofhalo, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, halo-(CH₂CH₂)₁₋₆—; halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— and halo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—.

In another variation of the above, X is a bond or is selected from thegroup consisting of C₁₋₆alkylenyl, —C(O)—, —C(O)O—;

Y is a bond or is selected from the group consisting of amino, halo,hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀-arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy andheteroaryloxy when R¹¹ is absent; and

R⁵ and R⁶ are each independently hydrogen or are each independentlyselected from the group consisting of halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O—,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-and halo-C₁₋₅alkylNR¹⁰C(O)—.

In a particular variation of each of the above embodiments, aspects andvariations, all of the variables R¹ to R¹² are not all hydrogens. In aparticular variation of each of the above, the halo group is fluorine.In another variation of each of the above, the radionuclide is ¹⁸F or¹¹C.

In another embodiment, there is provided a pharmaceutical compositionfor in vivo imaging of amyloid deposits, comprising (a) a compound ofany one of the above, and (b) a pharmaceutically acceptable carrier. Inanother embodiment, there is provided a method of diagnosing Alzheimer'sDisease or a predisposition thereto in a mammal, the method comprising:a) administering to the mammal a diagnostically effective amount of aradiolabeled compound, wherein the compound passes the blood-brainbarrier and preferentially binds to a soluble AD oligomers, polymers andfibrils in a brain tissue and wherein the compound is selected from thegroup consisting of radiolabeled flavones, coumarins, carbazoles,quinolinones, chromenones, imidazoles and triazoles and theirderivatives; b) allowing the compound to distribute into the braintissue; and c) imaging the brain tissue, wherein an increase in bindingof the compound to the brain tissue compared to a normal control levelof binding indicates that the mammal is suffering from or is at risk ofdeveloping Alzheimer's Disease. In one variation of the above method,the compound is a compound of any one of the above disclosed compounds.

In another embodiment, there is provided a method of diagnosingAlzheimer's Disease or a predisposition thereto in a mammal, the methodcomprising: a) administering to the mammal a diagnostically effectiveamount of a radiolabeled compound or composition of any one of theabove, wherein the compound passes the blood-brain barrier andpreferentially binds to a soluble AD oligomers, polymers and fibrils ina brain tissue; b) allowing the compound to distribute into the braintissue; and c) imaging the brain tissue, wherein an increase in bindingof the compound to the brain tissue compared to a normal control levelof binding indicates that the mammal is suffering from or is at risk ofdeveloping Alzheimer's Disease. In one variation of the above method,wherein the radiolabeled compound preferentially binds to fibrils. Inanother variation of the above, the brain tissue comprises afrontotemporal region or the hippocampal region. In a particularvariation of the above method, the increase in binding is at least 10%greater than said normal control value. In another variation of each ofthe above methods, the compound is administered by intravenousinjection.

In another embodiment, there is provided a method for detectingAlzheimer's Disease or a predisposition thereto in a living brain of amammal, the method comprising: a) administering the mammal with adiagnostically effective amount of a radiolabeled compound that passesthe blood-brain barrier and preferentially binds to a soluble ADoligomers, polymers and fibrils in the brain, wherein thedetectably-labeled compound is a compound of any one of the above; b)allowing the compound to distribute into the brain tissue; and c)imaging the brain tissue, wherein an increase in binding of the compoundto the brain tissue compared to a normal control level of bindingindicates that the mammal is suffering from or is at risk of developingAlzheimer's Disease.

In another embodiment, there is provided a method for detectingAlzheimer's Disease or a predisposition thereto in a living brain of amammal, the method comprising: a) administering the mammal with adiagnostically effective amount of a radiolabeled compound of any one ofthe above, wherein the compound passes the blood-brain barrier andpreferentially binds to a soluble AD oligomers, polymers and fibrils inthe brain; b) allowing the compound to distribute into the brain tissue;and c) imaging the brain tissue, wherein an increase in binding of thecompound to the brain tissue compared to a normal control level ofbinding indicates that the mammal is suffering from or is at risk ofdeveloping Alzheimer's Disease.

In another embodiment, there is provided a method of diagnosingAlzheimer's Disease or a predisposition thereto in a mammal, the methodcomprising: a) administering to the mammal a diagnostically effectiveamount of a radiolabeled compound, wherein the compound passes theblood-brain barrier and preferentially binds to a soluble or insolubleAD oligomers, polymers, fibrils, hyperphosphorylated tau,neurofibrillary tangles, paired helical filaments and/or neurotoxicsoluble oligomers in a brain, and wherein the radiolabeled compound is acompound as disclosed herein; and (b) employing a nuclear imagingtechnique selected from the group consisting of positron emissiontomography (PET) and single photon emission computed tomography (SPECT)for monitoring or visualizing a distribution of the radiolabeledcompound within the brain or within a portion thereof. In one variationof the above method, the radiolabeled compound or a derivative thereof,is a compound of any one of the above compounds. In yet anotherembodiment, there is provided a method for treating a disease orcondition, in a mammal in need thereof, selected from the groupconsisting of anxiety, depression, schizophrenia, Alzheimer's Disease,stress-related disease, panic, a phobia, obsessive compulsive disorder,obesity, post-traumatic stress syndrome, or epilepsy comprisingadministering to the mammal a therapeutically effective amount of acompound of any one of the above. In one variation, the compound is anon-radiolabeled compound of any one of the above compounds. In anothervariation, the compound is administered rectally, topically, orally,sublingually or parenterally. In one variation, the compound isadministered from about 0.001 to about 100 mg/kg of body weight of themammal per day. In another variation, the compound is administered fromabout 0.1 to about 50 mg/kg of body weight of the mammal per day. Inanother variation of each of the above methods, the compound is selectedfrom the group consisting of flavones, coumarins, carbazoles,quinolinones, chromenones, imidazoles and triazoles and theirderivatives.

In one aspect, for the methods of detection that accurately detect earlyonset AD prior to clinical symptomology, the focus may be directed totargeting senile plaque precursors, rather than the plaques and/orfibrils themselves. Accordingly, a potentially more effective strategyfor detecting and possibly treating AD, would rely on the detection ofbiomarkers such as neurotoxic soluble oligomers, which are linked toAD-related synaptic and neuronal damage, rather than the late-stageplaque, and fibril biomarkers associated with fully advanced AD.

TABLE 1 Known AD positive fluorescent dyes and imaging agents BindingName Compound and Reference Target Affinity Congo Red

Aβ monomer IC₅₀: 2-10 uM Curcumin

Aβ monomer IC₅₀: 10-20 uM ANS

Aβ monomer IC₅₀: >100 uM Thioflavin T

Aβ monomer IC₅₀: >500 uM Iodinated Flavone

Aβ40 aggregates Ki = 13 nM (—NMe2) to 72 nM (—OH) Pyridyl Styrene

Aβ fibrils Kd = 7.5-9 nM Diaryl acetylenes

Aβ plaques Kd = ~10 nM Thiophene chalcones

Aβ 1-42 aggregates Ki = 3.9-14 nM Aurones

Aβ 1-42 aggregates Ki = 1.24 nM PIB

Aβ fibrils Ki = 2.8 nM

An assay was developed using a Biacore instrument that introducedscreening ligands over gold-surface immobilized target proteins andmeasured the resultant rates of association and disassociation in orderto screen various compounds that bind to soluble AD oligomers, polymersand fibrils. In FIG. 1, the left hand portion of the curve representsthe binding of ligands to a specific substrate. The right portion of thecurve represents the dissociation of the ligand from the substrate.Ligands that associated quickly and dissociated slowly, relative to acontrol ligand, were considered hits.

Several hundred compounds were screened in a similar fashion and severalcommon classes of compounds were identified as hits falling into sevencommon chemotypes: flavones, coumarins, carbazoles, quinolinones,chromenones, imidazoles and triazoles (FIG. 2).

From the screening library, 38 compounds were identified as binders toAβ42 oligomers/soluble polymers (Table 2). Among these 38 compounds, 23compounds bound to Aβ42 synthetic fibrils. Several compounds belongingto the flavone and coumarin architectures, bound very strongly tooligomers, polymers and fibrils. Chromenes, carbazoles and diaryltriazoles were found to bind to oligomers and polymers preferentiallyover fibrils. Several of these compounds can be prepared as radiolabeledanalogs for use in detecting biomarkers in patients with AD.

TABLE 2 Compounds identified as binders to oligomers, polymers and/orfibrils. BINDING LEVELS TO Aβ₍₁₋₄₂₎ Oligomers/Polymers Aβ₍₁₋₄₂₎ Fibrils#25: 5-Amino-2-(trifluoromethyl)benzimidazole

++ + #40: 6-Hydroxyflavone

++ + #41: 7-Hydroxyflavone

+ + #42: 3,6-Dihydroxyflavone

+++ ++ #44: Fisetin

++++++ +++++ #51: 5-methoxyflavone

+ − #54: Harmol

++ + #55: 2-Hydroxycarbazole

+++ + #73: 7,8-Dihydroxy-4-phenylcoumarin

+++++ +++ #75: 7-Hydroxy-4-methyl-3-phenylcoumarin

+ − #84: 1-Chloro-4-hydroxyisoquinoline

+ − #89: 2-(5-Isoxazolyl)-4-methylphenol

+ + #97: 1-Methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinol

++ + #162: 5-Amino-8-hydroxyquinoline

++ + #194: 7-Hydroxy-2-methyl-3-(4-phenyl-4H-1,2,4-triazol-3-

++ + #197: 7-Ethoxy-2-methyl-3-phenoxy-4H-chromen-4-one

+ + #199: 3-(4-Ethoxyphenoxy)-7-hydroxy-2-methyl-4H-chromen-

+ − #200: 6-Ethyl-3-(4-fluorophenyl)-7-hydroxy-2-methyl-4H-c

+ − #201: 7,8-Dimethoxy-2-methyl-3-phenyl-4H-chromen-4-one

+ − #202: 7-Hydroxy-2,8-dimethyl-3-(4-phenyl-4H-1,2,4-triazo

++ − #203: 3-Hydroxy-2-phenylquinolin-4(1H)-one

++++ ++ #204: 7-Hydroxy-3-methyl-2-phenyl-4H-chromen-4-one

+ + #205: 2-(3,4-Dimethoxyphenyl)-3,6-dimethoxy-4H-chromen-4

+++ + #206: 3,7-Dimethoxy-2-(3-methoxyphenyl)-4H-chromen-4-one

+ − #207: 3,6-Dihydroxy-2-(3-hydroxyphenyl)-4H-chromen-4-one

++++ ++ #209: 3-(4-Fluorophenyl)-7-hydroxy-2-methyl-4H-chromen-4

+ + #214: 2-(Furan-2-yl)-3-methoxy-4H-chromen-4-one

+ + #216: 2-(Furan-2-yl)-3-hydroxy-6,8-dimethyl-4H-chromen-4

+ − #217: 3-Hydroxy-6,8-dimethyl-2-(thiophen-2-yl)-4H-chrome

+ − #236: A4B6

+ + #237: A4B7

+ − #238: A5B2

+ − #239: A5B4

++++ − #6: A2B5

+ + #261: 4-(4-(4-Fluorophenyl)-2-(4-nitrophenyl)-1H-imidazo

+ − #262: 4-(4-(4-Fluorophenyl)-2-(4-(methylsulfinyl)phenyl)

++ + #263: 4-(5-(4-Fluorophenyl)-4-(pyridin-4-yl)-1H-imidazol

++ ++ #268: 2-(4-Fluorophenyl)-4,5-diphenyl-1H-imidazole

+/− − A “+” sign represents a hit and the increase in “+” signs relatesto increasing binding affinity. A “−” sign represents no binding.

Table 3 provides examples of imaging agents derived from the hitscaffolds. Fluorides are shown in the structures as equivalent to¹⁸F-fluoride and methyl groups are equivalent to ¹¹C-carbon methylgroups.

TABLE 3 Examples of radiolabeled analogs useful for detecting ADbiomarkers in vivo. Chemical Name Structure Formula MW Code 2-(2-fluoroethoxy)- 9H-carbazole

C₁₄H₁₂FNO 229.25 CB-001 9-(2- fluoroethyl)-9H- carbazole-2-ol

C₁₄H₁₂FNO 229.25 N-(2- fluoroethyl-7- (2-(2-(2- methoxyethoxy)ethoxy)ethoxy)- 9H-carbazol-3- amine

C₂₁H₂₇FN₂O₄ 390.45 7-(2- fluoroethoxy)- N,N-dimethyl- 9H-carbazol-2-amine

C₁₆H₁₇FN₂O 272.32 7-(2-(2-(2- fluoroethoxy)- ethoxy)ethoxy)-N-methyl-9H- carbazol-3- amine

C₁₉H₂₃FN₂O₃ 346.40 CB-008 1-(3,6-diamino- 9H-carbazol-9- yl)-3-(2-(2-(2-fluoroethoxy)- ethoxy)ethoxy)- propan-1-one

C₂₁H₂₆FN₃O₄ 403.45 N-(2- fluroethyl)-2- hydroxy-11H- benzo[a]carbazole-3-carboxamide

C₁₉H₁₅FN₂O₂ 322.33 2-(6-chloro-9H- carbazol-2-yl)- N-(2-fluoro-ethyl)propanamide

C₁₇H₁₆ClFN₂O 318.77 2-(6-fluoro-9H- carbazol-2-yl)- N,N-dimethyl-propanamide

C₁₇H₁₇FN₂O 284.33 2-methoxy-9H- carbazole

C₁₃H₁₁NO 197.23 6-iodo-2- methoxy-9H- carbazole

C₁₃H₁₀INO 323.13 7-(2- fluoroethoxy)- N,N-dimethyl- 9H-carbazol-2- amine

C₁₆H₁₇FN₂O 272.32 tert-butyl 2-(2-(2- (2-fluoroethoxy)- ethoxy)ethoxy)-9H-carbazole-9- carboxylate

C₂₃H₂₈FNO₅ 417.47 CB-005 2-(2-(2-(2- fluoroethoxy)- ethoxy)ethoxy)-9-methyl-9H- carbazole

C₁₉H₂₂FNO₃ 331.38 CB-006 7-(2-(2-(2- fluoroethoxy- ethoxy)ethoxy)-N,N-dimethyl- 9H-carbazol-2- amine

C₂₀H₂₅FN₂O₃ 360.42 CB-007 N-(7-(2-(2-(2- fluoroethoxy)- ethoxy)ethoxy)-9H-carbazol-2- yl)acetamide

C₂₀H₂₃FN₂O₄ 374.41 CB-009 7-(2-(2-(2- fluoroethoxy)- ethoxy)ethoxy)-9H-pyrido[2,3- b]indole

C₁₇H₁₉FN₂O₃ 318.34 CB-028 2-(2-(2-(2- fluoroethoxy)- ethoxy)ethoxy)-9H-carbazole

C₁₈H₂₀FNO₃ 317.35 CB-003 7-(2-(2-(2- fluoroethoxy)- ethoxy)ethoxy)-N-methyl-9H- carbazol-2- amine

C₁₉H₂₃FN₂O₃ 346.40 CB-004 N-(7-(2-(2-(2- fluoroethoxy)- ethoxy)ethoxy)-9H-carbazol-2- yl)formamide

C₁₉H₂₁FN₂O₄ 360.38 CB-010 6-(2-(2-(2- fluoroethoxy)- ethoxy)ethoxy)-9-(methoxymethyl)- N,N-dimethyl- 9H-carbazol-3- amine

C₂₂H₂₉FN₂O₄ 404.48 CB-011 N-(7-(2- fluoroethoxy)- 9H-carbazol-2-yl)formamide

C₁₅H₁₃FN₂O₂ 272.27 CB-012 N-(7-(2-(2- fluoroethoxy)- ethoxy)-9H-carbazol-2- yl)formamide

C₁₇H₁₇FN₂O₃ 316.33 CB-024 N-(2-fluoroethyl)- 6-methoxy-9H- carbazol-3-amine

C₁₅H₁₅FN₂O 258.29 CB-013 7-((4- fluorobutyl)- (methyl)amino)-9H-carbazol-2-ol

C₁₇H₁₉FN₂O 286.34 CB-014 7-((2- fluoroethyl)- (methyl)amino)-9H-carbazol-2-ol

C₁₅H₁₅FN₂O 258.29 CB-015 7-(2-fluoro- ethylamino)-9H- carbazol-2-ol

C₁₄H₁₃FN₂O 244.26 CB-016 7-((2-(2-(2- fluoroethoxy)- ethoxy)ethyl)-(methyl)amino)- 9H-carbazol-2-ol

C₁₉H₂₃FN₂O₃ 346.40 CB-019 7-(2- fluoroethoxy)- N-methyl-9H- carbazol-2-amine

C₁₅H₁₅FN₂O 258.29 CB-020 7-(2-fluoro- ethoxy)-9H- carbazol-2-ol

C₁₄H₁₂FNO₂ 245.25 CB-025 7-(2-(2-(2- fluoroethoxy)- ethoxy)ethoxy)-9H-carbazol-2-ol

C₁₈H₂₀FNO₄ 333.35 CB-026 N-(4-(7-amino- 9H-carbazol-2- yloxy)phenyl)-2-fluoropropanamide

C₂₁H₁₈FN₃O₂ 363.38 CB-027 1-(2-(2-(2-(2- fluoroethoxy)- ethoxy)ethoxy)-9H-carbazol-9- yl)ethanone

C₂₀H₂₂FNO₄ 359.39 CB-017 (2-(2-(2-(2- fluoroethoxy)- ethoxy)ethoxy)-9H-carbazol-9- yl)(phenyl)- methanone

C₂₅H₂₄FNO₄ 421.46 CB-021 2-fluoro-N-(4-(7- (methylamino)- 9H-carbazol-2-yloxy)phenyl)- propanamide

C₂₂H₂₀FN₃O₂ 377.41 CB-029 N-(7-(4- fluorobutoxy)- 9H-carbazol-2-yl)formamide

C₁₇H₁₇FN₂O₂ 300.33 CB-030 tert-butyl 2-(2-(2- (2-fluoroethoxy)-ethoxy)ethoxy)- 9H-pyrido[2,3- b]indol-7- ylcarbamate

C₂₂H₂₈FN₃O₅ 433.47 CB-031 2-(2-(2-(2- fluoroethoxy)- ethoxy)ethoxy)-9H-pyrido[2,3- b]indol-7-amine

C₁₇H₂₀FN₃O₃ 333.36 CB-032 7-(benzyloxy)- N-(2-fluoroethyl)- N-methyl-9H-carbazol-2- amine

C₂₂H₂₁FN₂O 348.41 CB-033 2-(2-(2-(2- fluoroethoxy)- ethoxy)ethoxy)-N-methyl-9H- pyrido[2,3- b]indol-7-amine

C₁₈H₂₂FN₃O₃ 347.38 CB-034 6-bromo-9H- carbazol-2-ol

C₁₂H₈BrNO 262.10 8-(2- fluoroethoxy)-7- hydroxy-4- phenyl-2H-chromen-2-one

C₁₇H₁₃FO₄ 300.28 2-(4-(2- fluoroethoxy)-3- hydroxyphenyl)-3,7-dihydroxy-4H- chromen-4-one

C₁₇H₁₃FO₆ 332.28 7-(2- fluoroethoxy)-8- hydroxy-4- phenyl-2H-chromen-2-one

C₁₇H₁₃FO₄ 300.28 4-(4-(2-fluoro- ethoxy)phenyl)- 7,8-dihydroxy-2H-chromen-2-one

C₁₇H₁₃FO₅ 316.28 4-(4-(2- fluoroethylamino)- phenyl)-7,8- dihydroxy-2H-chromen-2-one

C₁₇H₁₄FNO₄ 315.30 4-(3,4-dihydroxy- phenyl)-7-(2- fluoroethoxy)-8-hydroxy-2H- chromen-2-one

C₁₇H₁₃FO₆ 332.28 7-(2-(2-(2-fluoro- ethoxy)ethoxy)- 8-hydroxy-4-(4-hydroxyphenyl)- 2H-chromen-2-one

C₂₁H₂₁FO₇ 404.39 6-(2- fluoroethoxy)-3- hydroxy-2- phenylquinolin-4(1H)-one

C₁₇H₁₄FNO₃ 299.30 1-(2- fluoroethyl)-3,6- dihydroxy-2- phenylquinolin-4(1H)-one

C₁₇H₁₄FNO₃ 299.30 2-(3-(2- fluoroethoxy)-4- hydroxyphenyl)-3,6-dihydroxy- quinolin-4(1H)-one

C₁₇H₁₄FNO₅ 331.30 2-(4-(2-(2-(2- fluoroethoxy)- ethoxy)ethoxy)-3-hydroxyphenyl)- 3,6-dihydroxy- quinolin-4(1H)-one

C₂₁H₂₂FNO₇ 419.40 2-(3,4-dihydroxy- phenyl)-3-hydroxy- 6-(methylamino)-quinolin-4(1H)-one

C₁₆H₁₄N₂O₄ 298.29 1-(2-fluoroethyl)- 3,6-dihydroxy-2- (4-hydroxyphenyl)quinolin-4(1H)-one

C₁₇H₁₄FNO₄ 315.30 7-(2-(4-(2- fluoroethyl)-1H- 1,2,3-triazol-1-yl)ethoxy)-8- hydroxy-4- phenyl-2H- chromen-2-one

C₂₁H₁₈FN₃O₄ 395.38 1-(2,4- dimethylphenyl)- 4-(3-fluoro-5-methylphenyl)- 1H-1,2,3-triazole

C₁₇H₁₆FN₃ 281.33Synthesis of Ligands and their Labeling Precursors:

Halogenation and Radiohalogenation:

As disclosed herein, for a number of different AD ligands, such asflavones, coumarins, carbazoles, quinolinones, chromenones,trisubstituted imidazoles and their derivatives as disclosed herein, theradiolabeled atom, such as a halogen atom, for example, may be readilyintroduced into the ligand using a number of different methods wellknown in the art. Accordingly, the radiolabeled compounds of the FormulaIto Formula VI of the present application may be prepared using standardmethods known in the art for preparing such radiolabeled compoundshaving a particular substituent, wherein the compound may beincorporated with a particular radionuclide selected from the groupconsisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br.

In one particular example, the halogen may be introduced by a methodusing a tin for halogen exchange process. For example, a non-radioactivehalogen such as iodine, may be replaced by an organo tin compound via ametal, such as a palladium composition, to form the radiolabeling tinprecursor, as represented below. This precursor is then subjected toradioactive halogenation via displacement with Na¹²⁵I source, forexample, to afford the radioactive ligand.

Alternatively, the radio labeled halogen may be readily introduced viadirect halogenation. For example, for a ligand comprising an aromaticring as part of the scaffold, or an aromatic substituent of a ligand,the aromatic ring may be directly iodinated using well-establishedradioiodination procedure. One such example is represented below using acarbazole ligand.

For ¹¹C-labeled compounds, the labeled compound may be prepared by thealkylation or methylation of a hydroxyl group, such as with [¹¹C]CH₃I toprovide the corresponding C-11 labeled methoxy derivative. For example,such a process is represented by the reaction of the flavone derivativeshown below.

Other methods of preparing radiolabeled ligands are well known in theart. Example of such methods are disclosed in, for example: 1) Jewett,D. M. (1992) A Simple Synthesis of [¹¹C]Methyl Triflate Appl. Radiat.Isot. 43, 1383-1385; 2) Crouzel, C. Langstrom, B., Pike, V. W., andCoenen, H. H. (1987) Recommendations for a practical production of[¹¹C]methyl iodide Appl. Radiat. Isot. Int. J. Appl. Instrum. Part A 38,601-603; Dannals, R. F., Ravert, H. T.; 3) Wilson, A. A. (1990)Radiochemistry of Tracers for Neurotransmitter Receptor Studies. In:Quantitative Imaging: Neuroreceptors, Neurotransmitters, and Enzymes.(Edited by Frost, J. J. Wagner Jr., H. N. pp. 19-35, Raven Press, NewYork; 4) Jewett, D. M., Manger, T. J., and Watkins, G. L. (1991) CaptiveSolvent Methods for Fast Simple Carbon-11 Radioalkylations. In: NewTrends in Radiopharmaceutical Synthesis, Quality Assurance andRegulatory Control (Edited by Emran, A. M.) pp. 387-391. Plenum Press,New York; 5) Marazano, C., Maziere, M., Berger, G., and Comar, D. (1977)Synthesis of methyl iodide-¹¹C and formaldehyde-¹¹C Appl. Radiat. Isot.28, 49-52; 6) Watkins, G., Jewett, D., Mulholland, G., Kitbourn, M., andToorongian, S. (1988) A Captive Solvent Method for RapidN-[¹¹C]Methylation of Secondary Amides: Application to theBenzodiazepine, 4′-Chlorodiazepam (RO5-4864) Appl. Radiat. Isot. 39,441-444; and 7) Wilson, A. A., DaSilva, J. N., and Houle, S. (1996) Invivo evaluation of [¹¹C] and [¹⁵F]-labelled cocaine analogues aspotential dopamine transporter ligands for positron emission tomographyNucl. Med. Biol. 23, 141-146. The subject matter of all references citedherein are incorporated herein by reference in their entirety.

Synthesis of AD-CB-WZ01013

To hydroxycarbazole (73 mg, 0.4 mmol) in 1 mL of NMP was added Cs₂CO₃(130 mg, 0.4 mmol) and bromofluoroethane (51 mg, 0.4 mmol). The mixturewas stirred at rt for 15 h and diluted with Et₂O (50 mL). It was washedwith 1 M HCl (30 mL) and water (2×40 mL), dried over MgSO₄ andconcentrated. The crude product was purified with silica chromatography(4% EtOAc in hexane to 25%) to afford the desired product (36 mg) as anoff-white solid.

¹H NMR (400 MHz, CDCl₃/acetone-d₆) δ 9.98 (s, 1H), 7.95 (t, J=8.8 Hz,2H), 7.40 (d, J=8.0 Hz, 1H), 7.28 (t, J=8 Hz, 1H), 7.13 (t, J=8.0 Hz,1H), 7.00 (d, J=2 Hz, 1H), 6.83 (dd, J=8.8, 2.0 Hz, 1H), 4.85 (t, J=4Hz, 1H), 4.73 (t, J=4 Hz, 1H), 4.35 (t, J=4 Hz, 1H), 4.28 (t, J=4 Hz,1H); MS (ESI) m/z 230 (M+H⁺).

Synthesis of AD-C-WZ01011

To hydroxycarbazole (183 mg, 1 mmol) in 4 mL of NMP was added Cs₂CO₃(326 mg, 1 mmol) and ethylenedi-tosylate (370 mg, 1 mmol). The mixturewas stirred at rt for 15 h and diluted with Et₂O (80 mL). It was washedwith 1 M HCl (50 mL) and water (2×50 mL), dried over MgSO₄ andconcentrated. The crude product was purified with silica chromatography(50% DCM in hexane to 100% DCM) to afford the desired product (75 mg) asan off-white solid.

¹H NMR (400 MHz, acetone-d₆) δ 10.21 (s, 1H), 8.00 (d, J=8.0 Hz, 1H),7.95 (d, J=8.4 Hz, 1H), 7.84 (d, J=8.4 Hz, 2H), 7.45 (m, 3H), 7.30 (t,J=8.0 Hz, 1H), 7.13 (t, J=8.0 Hz, 1H),); 6.98 (s, 1H), 6.73 (d, J=8.4Hz, 1H), 4.44 (t, J=4.0 Hz, 2H), 4.30 (t, J=4.0 Hz, 2H), 2.42 (s, 3H);MS (ESI) m/z 382 (M+H⁺), 404 (M+Na⁺).

Synthesis of 18F-labeled AD-CB-001P-WZ-01019([¹⁸F]2-(2-Fluoro-ethoxy)-9H-carbazole)

[¹⁸F]Fluoride (600-900 mCi) as an enriched solution in H₂ ¹⁸O wasdelivered to the synthesis module. The [¹⁸F]fluoride was trapped on anion-exchange column and then eluted into the reaction vessel usingaqueous potassium carbonate (3.0 mg in 0.4 mL H₂O). Kryptofix-2.2.2phase transfer reagent was added (20.0 mg in 1.0 mL MeCN) and thewater-acetonitrile azeotrope was evaporated to dryness.Toluene-4-sulfonic acid 2-(9H-carbazol-2-yloxy)-ethyl ester precursor (4mg in 0.9 mL MeCN/0.1 mL DMSO) was added to the reactor and then thefluorination reaction was heated at 115° C. for 10 min. The crudereaction mixture was then purified by semi-preparative HPLC (Column:Phenomenex Luna C-18, 250 mm×10 mm; Mobile-Phase Gradient 95:5 H₂0(+0.05% TFA): MeCN (+0.05% TFA) to 100% MeCN (+0.05% TFA); Flow rate: 5mL/min).

The peak corresponding to [¹⁸F]2-(2-fluoro-ethoxy)-9H-carbazole wascollected and simultaneously diluted with sterile water (10 mL). Theresulting mixture was passed over a C-18 Sep-Pak so that the product wastrapped and residual acetonitrile was washed away with further water (10mL). [¹⁸F]2-(2-Fluoro-ethoxy)-9H-carbazole was then eluted into theproduct vial with USP grade ethanol (0.5 mL) and diluted with sterilewater (9.5 mL) to provide a final formulation (19-34 mCi in 10 mL)suitable for injection (7.5% decay corrected yield, 100% radiochemicalpurity).

Purity was determined by analytical HPLC equipped with a radioactivitydetector and identity was confirmed by comparison with HPLC data for thecorresponding unlabeled reference standard (FIG. 3A and FIG. 3B).

Synthesis of AD-CB-002P-WZ01031

To hydroxycarbazole (92 mg, 0.5 mmol) in 2 mL of NMP was added Cs₂CO₃(163 mg, 0.5 mmol) and azido ethyltosylate (121 mg, 0.5 mmol). Themixture was stirred at rt for 15 h and diluted with Et₂O (50 mL). It waswashed with 0.5 M HCl (50 mL) and water (2×50 mL), dried over MgSO₄ andconcentrated. The crude product was purified with silica chromatography(80% DCM in hexane to 100% DCM) to afford the desired product (76 mg) asa white solid.

¹H NMR (400 MHz, CDCl₃/acetone-d₆) δ 9.98 (s, 1H), 7.95 (m, 2H), 7.41(d, J=8.4 Hz, 1H), 7.29 (t, J=8.0 Hz, 1H), 7.14 (t, J=8.0 Hz, 1H),);7.01 (s, 1H), 6.84 (d, J=8.4 Hz, 1 H), 4.28 (t, J=4.8 Hz, 2H), 3.67 (t,J=4.8 Hz, 2H); MS (ESI) m/z 253 (M+H⁺).

Synthesis of AD-CB-002S-WZ01033

To azido carbazole (32 mg, 0.127 mmol) in 0.5 mL of DMF was added CuI(7.6 mg, 0.04 mmol), DIPEA (16.4 mg, 0.127 mmol), and fluoropentyne(16.4 mg, 0.19 mmol). The reaction mixture was vigorously stirred for 1h and diluted with EtOAc (30 mL). It was washed with water (50 mL), 0.5M HCl (30 mL), water (2×50 mL), dried over MgSO₄ and concentrated. Thecrude product was pre-absorbed on silica (3 g) and loaded on a 4 gsilica column and eluted with 30% EtOAc in hexane to 50% to afford thedesired compound (20 mg).

¹H NMR (400 MHz, CDCl₃/CD₃OD) δ 7.95 (d, J=7.6 Hz, 1H), 7.91 (d, J=8.4Hz, 1 H), 7.76 (s, 1H), 7.40 (d, J=8.0 Hz, 1H), 7.31 (t, J=7.6 Hz, 1H),7.14 (t, J=7.6 Hz, 1H), 6.94 (d, J=2.4 Hz, 1H), 6.78 (dd, J=8.8, 2.4 Hz,1H), 4.83-4.78 (m, 2H), 4.53-4.48 (m, 3H), 4.40 (t, J=6.0 Hz, 1H), 2.85(t, J=7.6 Hz, 2H), 2.10-1.99 (m, 2H); MS (ESI) m/z 339 (M+H⁺).

Synthesis of 18F-labeled AD-CB-002S-WZ01033: Preparation of [¹⁸F]5-Fluoro-pent-1-yne

[¹⁸F]Fluoride (600-900 mCi) as an enriched solution in H₂ ¹⁸O isdelivered to the synthesis module. The [¹⁸F]fluoride is trapped on anion-exchange column and then eluted into the reaction vessel usingaqueous potassium carbonate (3.0 mg in 0.4 mL H₂O). Kryptofix-2.2.2phase transfer reagent is added (20.0 mg in 1.0 mL MeCN) and thewater-acetonitrile azeotrope is evaporated to dryness.

Toluene-4-sulfonic acid pent-4-ynyl ester (20 mg in 0.8 mL MeCN) isadded to the reactor and the fluorination reaction is heated at 110° C.for 5 min. Following fluorination, the crude reaction mixture ispurified by distillation and yields [¹⁸F] 5-fluoro-pent-1-yne as asolution in acetonitrile (trapped at −78° C. due to the volatility ofthe product).

Preparation of Triazole:

A mixture of azide precursor (5 mg), sodium ascorbate (40 mg),tris-(benzyltriazolylmethyl)amine (TBTA, 25 mg) and aqueous coppersulfate solution (0.1 M, 0.25 mL) in DMF (0.4 mL) and water (0.1 mL) isadded to the cooled pentyne solution described above. The reactionmixture is then warmed to rt and stirred for 30 min. After this time,the reaction is purified by semi-preparative HPLC. The peakcorresponding to the product is collected and simultaneously dilutedwith sterile water (10 mL). The resulting mixture is passed over a C-18Sep-Pak and residual acetonitrile is washed away with additional water(10 mL). The product is eluted into the product vial with USP gradeethanol (0.5 mL) and diluted with sterile water (9.5 mL) providing afinal formulation suitable for injection.

Purity is determined by analytical HPLC equipped with a radioactivitydetector and identity is confirmed by comparison with HPLC data for thecorresponding unlabeled reference standard.

Synthesis of ¹⁸F-Labeled CB-003

[¹⁸F]Fluoride (600-900 mCi) as an enriched solution in H₂ ¹⁸O isdelivered to the synthesis module. The [¹⁸F]fluoride is trapped on anion-exchange column and then eluted into the reaction vessel usingaqueous potassium carbonate (3.0 mg in 0.4 mL H₂O). Kryptofix-2.2.2phase transfer reagent is added (20.0 mg in 1.0 mL MeCN) and thewater-acetonitrile azeotrope is evaporated to dryness. The precursor (4mg in 0.9 mL MeCN/0.1 mL DMSO) is added to the reactor and thefluorination reaction is heated at 115° C. for 10 min. The mixture wascooled to 55° C. and most of the acetonitrile was evaporated undervacuum and a stream of argon as before. To the crude Boc-protectedproduct was added aqueous hydrochloric acid (1.0 m, 1.0 mL), and themixture was heated to 105° C. for 3 minutes. After cooling to 35° C.,aqueous sodium acetate (2.0 M, 0.5 mL) was added with stirring. Thecrude reaction mixture is then purified by semi-preparative HPLC(Column: Phenomenex Luna C-18, 250 mm×10 mm; Mobile-Phase Gradient 95:5H₂0 (+0.05% TFA): MeCN (+0.05% TFA) to 100% MeCN (+0.05% TFA); Flowrate: 5 mL/min; time=25 min). The peak corresponding to the finalproduct is collected and simultaneously diluted with sterile water (10mL). The resulting mixture is passed over a C-18 Sep-Pak so that theproduct is trapped and residual acetonitrile is washed away with furtherwater (10 mL). The product is then eluted into the product vial with USPgrade ethanol (0.5 mL) and diluted with sterile water (9.5 mL) providinga final formulation suitable for injection (31% decay uncorrected yield,100% radiochemical purity). Purity was determined by analytical HPLCequipped with a radioactivity detector and identity was confirmed bycomparison with HPLC data for the corresponding unlabeled referencestandard.

Synthesis of ¹⁸F-Labeled CB-004

[¹⁸F]Fluoride (600-900 mCi) as an enriched solution in H₂ ¹⁸O isdelivered to the synthesis module. The [¹⁸F]fluoride is trapped on anion-exchange column and then eluted into the reaction vessel usingaqueous potassium carbonate (3.0 mg in 0.4 mL H₂O). Kryptofix-2.2.2phase transfer reagent is added (20.0 mg in 1.0 mL MeCN) and thewater-acetonitrile azeotrope is evaporated to dryness. The precursor (4mg in 0.9 mL MeCN/0.1 mL DMSO) is added to the reactor and thefluorination reaction is heated at 115° C. for 10 min. The mixture wascooled to 55° C. and most of the acetonitrile was evaporated undervacuum and a stream of argon as before. To the crude Boc-protectedproduct was added aqueous hydrochloric acid (1.0 M, 1.0 mL), and themixture was heated to 105° C. for 3 minutes. After cooling to 35° C.,aqueous sodium acetate (2.0 M, 0.5 mL) was added with stirring. Thecrude reaction mixture is then purified by semi-preparative HPLC(Column: Phenomenex Luna C-18, 250 mm×10 mm; Mobile-Phase Gradient 95:5H₂0 (+0.05% TFA): MeCN (+0.05% TFA) to 100% MeCN (+0.05% TFA); Flowrate: 5 mL/min; time=25 min). The peak corresponding to the finalproduct is collected and simultaneously diluted with sterile water (10mL). The resulting mixture is passed over a C-18 Sep-Pak so that theproduct is trapped and residual acetonitrile is washed away with furtherwater (10 mL). The product is then eluted into the product vial with USPgrade ethanol (0.5 mL) and diluted with sterile water (9.5 mL) providinga final formulation suitable for injection (3% decay uncorrected yield,100% radiochemical purity). Purity was determined by analytical HPLCequipped with a radioactivity detector and identity was confirmed bycomparison with HPLC data for the corresponding unlabeled referencestandard.

Synthesis of ¹⁸F-Labeled CB-007

[¹⁸F]Fluoride (600-900 mCi) as an enriched solution in H₂ ¹⁸O isdelivered to the synthesis module. The [¹⁸F]fluoride is trapped on anion-exchange column and then eluted into the reaction vessel usingaqueous potassium carbonate (3.0 mg in 0.4 mL H₂O). Kryptofix-2.2.2phase transfer reagent is added (20.0 mg in 1.0 mL MeCN) and thewater-acetonitrile azeotrope is evaporated to dryness. The precursor (4mg in 0.9 mL MeCN/0.1 mL DMSO) is added to the reactor and thefluorination reaction is heated at 115° C. for 10 min. The mixture wascooled to 55° C. and most of the acetonitrile was evaporated undervacuum and a stream of argon as before. To the crude Boc-protectedproduct was added aqueous hydrochloric acid (1.0 M, 1.0 mL), and themixture was heated to 105° C. for 3 minutes. After cooling to 35° C.,aqueous sodium acetate (2.0 M, 0.5 mL) was added with stirring. Thecrude reaction mixture is then purified by semi-preparative HPLC(Column: Phenomenex Luna C-18, 250 mm×10 mm; Mobile-Phase Gradient 95:5H₂0 (+0.05% TFA): MeCN (+0.05% TFA) to 100% MeCN (+0.05% TFA); Flowrate: 5 mL/min; time=25 min). The peak corresponding to the finalproduct is collected and simultaneously diluted with sterile water (10mL). The resulting mixture is passed over a C-18 Sep-Pak so that theproduct is trapped and residual acetonitrile is washed away with furtherwater (10 mL). The product is then eluted into the product vial with USPgrade ethanol (0.5 mL) and diluted with sterile water (9.5 mL) providinga final formulation suitable for injection (1.2% decay uncorrectedyield, 100% radiochemical purity). Purity was determined by analyticalHPLC equipped with a radioactivity detector and identity was confirmedby comparison with HPLC data for the corresponding unlabeled referencestandard.

Synthesis of ¹⁸F-Labeled CB-012

[¹⁸F]Fluoride (600-900 mCi) as an enriched solution in H₂ ¹⁸O wasdelivered to the synthesis module. The [¹⁸F]fluoride was trapped on anion-exchange column and then eluted into the reaction vessel usingaqueous potassium carbonate (3.0 mg in 0.4 mL H₂O). Kryptofix-2.2.2phase transfer reagent was added (20.0 mg in 1.0 mL MeCN) and thewater-acetonitrile azeotrope was evaporated to dryness.Toluene-4-sulfonic acid 2-(9H-carbazol-2-yloxy)-ethyl ester precursor (4mg in 0.9 mL MeCN/0.1 mL DMSO) was added to the reactor and then thefluorination reaction was heated at 115° C. for 10 min. The crudereaction mixture was then purified by semi-preparative HPLC (Column:Phenomenex Luna C-18, 250 mm×10 mm; Mobile-Phase Gradient 95:5 H₂0(+0.05% TFA): MeCN (+0.05% TFA) to 100% MeCN (+0.05% TFA); Flow rate: 5mL/min). The peak corresponding to the product was collected andsimultaneously diluted with sterile water (10 mL). The resulting mixturewas passed over a C-18 Sep-Pak so that the product was trapped andresidual acetonitrile was washed away with further water (10 mL).[¹⁸F]2-(2-Fluoro-ethoxy)-9H-carbazole was then eluted into the productvial with USP grade ethanol (0.5 mL) and diluted with sterile water (9.5mL) to provide a final formulation (19-34 mCi in 10 mL) suitable forinjection (2% decay uncorrected yield, 100% radiochemical purity).Purity was determined by analytical HPLC equipped with a radioactivitydetector and identity was confirmed by comparison with HPLC data for thecorresponding unlabeled reference standard.

Assays of Carbazole Derivatives:

From the Biacore assay, two carbazole derivatives displayed promisingbinding affinities to oligomers/polymers and fibrils (Table 4). Thebeta-carboline Harmol, a member of the harmala alkaloids, is the urinarymetabolite of harmine. The harmala alkaloids are MAO inhibitors and arecommonly found in Syrian rue, Peganum harmala, and the South Americanvine Banisteriopsis caapi, both of which are purported to possess stronghallucinogenic effects. The beta-carbolenes have a varied effect on thecentral nervous system including binding to the 5-HT₂, 5-HT_(1a),glutamate NMDA and imidazoline receptors; inhibiting MAO-A enzyme andinterfering with dopaminergic transmission. And while beta-carbolinesare thought to be cytotoxic, they also maintain neuroprotectiveproperties supposedly offering neuroprotection against dopamine andglutamate and, additionally, by scavenging reactive oxygen species. Arecent report demonstrated that beta-carboline alkyloids induce afacilitation of short and long term memory in object recognition tasksin mice, although the means by which the alkyloids are exerting theireffect is unclear. Moura, D. J., et al., Effects of b-carbolinealkaloids in the object recognition task in mice. Life Sciences, 2006,79: p. 2099-2104.

The second active carbazole discovered in the assay is2-hydroxycarbazole. 2-Hydroxycarbazole has been recently shown torelease Ca²⁺ ion from skeletal and cardiac muscle through a distinctpharmacological pathway. The generic carbazole scaffold exists inseveral therapeutics including the non-steroidal anti-inflammatorycarprofen, carazolol (a beta-blocker) and YM-53601 (a squalene synthaseinhibitor). Recent work has shown that carbazole derivatives can act asγ-secretase modulators. [Narlawar, R., et al., N-Substitutedcarbazolyloxyacetic acids modulate Alzheimer associated g-secretas.Bioorganic & Medicinal Chemistry Letters, 2007, 17: p. 176-182] Inanother AD related project, Howlett discovered highly elaboratedcarbazoles, such as carvedilol, inhibit fibril formation, albeit thebinding affinities to the fibrils were not determined. [Howlett, D. R.,et al., Common Structural Features Determine the Effectiveness ofCarvedilol, Daunomycin and Rotiletracycline as Inhibitors of Alzheimerb-Amyloid Fibril Formation. Biochemical Journal, 1999, 343: p. 419-423]Interestingly, an article intending to determine the practicality ofusing carbazoles as fibril inhibitors based on cell permeabilitysuggests that carbazoles are unlikely to cross the blood brain barrier,as they are PGP substrates, precluding their use as therapeutics forfibril inhibition. [Saengkhae, C., et al., Ability of Carbazole Salts,Inhibitors of Alzheimer b-Amyloid Fibril Formation, to Cross CellularMembranes. European Journal of Pharmacology, 2007, 559: p. 124-131]

By using an appropriate imaging modality, a tracer's biodistributionpattern becomes instantly visible and accessible. For example, by using¹⁸F-labeled tracers one can easily quantify a tracer's uptake into, andwashout from, the brain using positron emission tomography (PET).Tracers with high uptake and slow washout in normal brains generate lowsignal to noise ratios. Tracers with high uptake and fast washout innormal brains have high signal to noise rations and are consideredideal. ¹⁸F-labeled carbazoles possess ideal brain imaging properties.For example, an ¹⁸F-labeled carbazole was prepared and administered to anormal, white Sprague-Dawley rat (FIG. 6). Within minutes, the tracerentered into the brain and washed out over several minutes.

The non-radioactive carbazole also successfully competes off bothThioflavin T and FDDNP in brain tissue sections suggesting that thetracer binds to similar binding sites (FIGS. 4 and 5).

TABLE 4 Carbazole-based hits from the Biacore assay. Binding tooligomers/polymers Binding to fibrils (A(β-42) (Aβ1-42) #54: Harmol

++ + #55: 2-Hydroxycarbazole

+++ + #73: 7,8-Dihydroxy-4-phenylcoumarin A “+” sign represents a hitand the increase in “+” signs relates to increasing binding affinity. A“−” sign represents no binding.

A list of examples of carbazole-based imaging agents are shown in Table5. Many of the compounds are either ¹⁸F- or ¹¹C-labeled.

TABLE 5 Examples of carbazole-based imaging agents Mol. Compound NameStructure Formula Weight 2-(2-fluoroethoxy)-9H-carbazole

C₁₄H₁₂FNO 229.25 9-(2-fluoroethyl)-9H-carbazol-2-ol

C₁₄H₁₂FNO 229.25 N-(2-fluoroethyl)-7-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)- 9H-carbazol-3-amine

C₂₁H₂₇FN₂O₄ 390.45 7-(2-fluoroethoxy)-N,N- dimethyl-9H-carbazol-2-amine

C₁₆H₁₇FN₂O 272.32 7-(2-(2-(2- fluoroethoxy)ethoxy)ethoxy)-N-methyl-9H-carbazol-3-amine

C₁₉H₂₃FN₂O₃ 346.40 1-(3,6-diamino-9H-carbazol-9-yl)-3-(2-(2-(2-fluoroethoxy)- ethoxy)ethoxy)propan-1-one

C₂₁H₂₆FN₃O₄ 403.45 N-(2-fluoroethyl)-2-hydroxy-11H-benzo[a]carbazole-3-carboxamide

C₁₉H₁₅FN₂O₂ 322.33 2-(6-chloro-9H-carbazol-2-yl)-N-(2-fluoroethyl)propanamide

C₁₇H₁₆ClFN₂O 318.77 2-(6-fluoro-9H-carbazol-2-yl)-N,N-dimethylpropanamide

C₁₇H₁₇FN₂O 284.33 2-methoxy-9H-carbazole

C₁₃H₁₁NO 197.23 6-iodo-2-methoxy-9H-carbazole

C₁₃H₁₀INO 323.13Detailed Biacore assay protocol:

β-Amyloid (Aβ42) soluble aggregates (oligomers/soluble polymers).Biotin-LC-Aβ42 was mixed with Aβ42 at a ratio of 3:2. After dissolvingin 1% NH₄OH and dH₂O, the mixture (40 uM concentration) was incubated in1×PBS (pH 7.4) buffer at RT for 6-hours to form oligomers/solublepolymers. The free monomer of Aβ42 in the sample was removed using aMicrocon centrifugal filter tube with a 10 KDa of MW cutoff. TheBiotin-LC-Aβ42 oligomers/polymers were immobilized onto SA chip bystreptavidin-biotin capture.

β-Amyloid (Aβ42) insoluble aggregates (fibrils). Fibrils were preparedaccording to methods published previously (Agdeppa E D et al. 2001).Briefly, 0.5 mg of Aβ42 (Biotin-LC-Aβ42:Aβ42=1:1) was dissolved in 1 mlof PBS, pH 7.4, and mixed with a magnetic stir bar for 3 d at 37° C.,resulting in a visibly cloudy solution. The fibril pellet was collectedby centrifugation. The Biotin-LC-Aβ42 fibrils were immobilized onto SAchip by streptavidin-biotin capture.

Screening of amyloid binding compounds with Biacore (Surface PlasmonResonance Analysis). Aβ42 oligomers/soluble polymers or fibrils wereimmobilized on Flow Cell 2 (Fc2) or Flow Cell 3 (Fc3) of the SensorChip, with Fc1 serving as the control. Screening compounds at 10 uMconcentration was flown through Fc1, Fc2, and Fc3 for 2 minutes at aflow rate of 30 ul/minute. The Flow Cells were then washed with runningbuffer (1×PBS) for 2 minute, and regenerated with 50 mM of NaOH for 30seconds. The real time interaction between the screening compound andthe amyloid aggregates immobilized on the chip surface was recorded inthe sensorgram.

Immunostaining of brain sections with Thioflavin T. Brain samples fromdonors with Alzheimer disease were paraffin wax infiltrated afterfixation. Paraffin blocks with embedded brain samples were mounted ontomicrotome and sectioned. Sections were then deparaffinized and hydrated,followed by incubation with or without AD-CB-001S-WZ01013. Staining wascarried out with 1 uM Thioflavin T. Images were obtained with afluorescence microscope (FIG. 4).

Immunostaining of brain sections with FDDNP. Brain samples from donorswith Alzheimer disease were paraffin wax infiltrated after fixation.Paraffin blocks with embedded brain samples were mounted onto microtomeand sectioned. Sections were then deparaffinized and hydrated, followedby incubation with or without AD-CB-001S-WZ01013. Staining was carriedout with 1 uM FDDNP. Images were obtained with a fluorescence microscope(FIG. 5).

Imaging Results of AD-CB-001

A white Sprague-Dawley rat was injected via tail vein with ˜850 uCiAD-CB-001, formulated in 10% EtOH:water. A dynamic scan was conductedfor 30 min on a R4 microPET scanner. The data was reconstructed using 1min framing. Within minutes, the tracer entered the rat brain andquickly washed out (FIG. 6).

Preparation of Coumarin Derivatives:

To coumarin (120 mg, 0.5 mmol) in 2 mL of NMP was added Cs₂CO₃ (163 mg,0.5 mmol) and ethylenedi-tosylate (185 mg, 0.5 mmol). The mixture wasstirred at rt for 15 h and diluted with Et₂O (50 mL). It was washed with1 M HCl (50 mL) and water (2×50 mL), dried over MgSO₄ and concentrated.The crude product was purified with silica chromatography (DCM 100% andthen 0.3% MeOH in DCM) to afford the desired product (51 mg) as a clearoil.

¹H NMR (400 MHz, CDCl₃) δ 7.82 (d, J=8.4 Hz, 2H), 7.52 (m, 3H), 7.43 (m,2H), 7.37 (m, 3H), 6.75 (s, 1H), 6.71 (d, J=9.2 Hz, 1H), 6.23 (s, 1H),4.41 (t, J=4.4 Hz, 2H), 4.22 (t, J=4.4 Hz, 2H), 2.46 (s, 3H); MS (ESI)m/z 437 (M+H⁺).

Synthesis of AD-C-003S-WZ01041

To coumarin (238 mg, 1 mmol) in 4 mL of NMP was added Cs₂CO₃ (326 mg, 1mmol) and bromofluoroethane (152 mg, 1.2 mmol). The mixture was stirredat rt for 15 h and diluted with Et₂O (50 mL). It was washed with 1 M HCl(50 mL) and water (2×50 mL), dried over MgSO₄ and concentrated. Thecrude product was purified with silica chromatography (DCM 80% in hexaneto 100%) to afford the desired product (160 mg) as a white solid.

¹H NMR (400 MHz, acetone-d6) δ 7.60-7.56 (m, 5H), 7.43 (d, J=8.8 Hz,1H), 7.03 (d, J=2.4 Hz, 1H), 6.96 (dd, J=8.8, 2.4 Hz, 1H), 6.18 (s, 1H),4.91-4.89 (m, 1H), 4.79-4.77 (m, 1 H), 4.49-4.47 (m, 1H), 4.42-4.40 (m,1H); MS (ESI) m/z 285 (M+H⁺).

Synthesis of ¹⁸F-Labeled AD-C-003S-WZ01041

[¹⁸F]Fluoride (600-900 mCi) as an enriched solution in H₂ ¹⁸O isdelivered to the synthesis module. The [¹⁸F]fluoride is trapped on anion-exchange column and then eluted into the reaction vessel usingaqueous potassium carbonate (3.0 mg in 0.4 mL H₂O). Kryptofix-2.2.2phase transfer reagent is added (20.0 mg in 1.0 mL MeCN) and thewater-acetonitrile azeotrope is evaporated to dryness. The precursor (4mg in 0.9 mL MeCN/0.1 mL DMSO) is added to the reactor and thefluorination reaction is heated at 115° C. for 10 min. The crudereaction mixture is then purified by semi-preparative HPLC (Column:Phenomenex Luna C-18, 250 mm×10 mm; Mobile-Phase Gradient 95:5 H₂0(+0.05% TFA): MeCN (+0.05% TFA) to 100% MeCN (+0.05% TFA); Flow rate: 5mL/min; time=25 min).

The peak corresponding to the product is collected and simultaneouslydiluted with sterile water (10 mL). The resulting mixture is passed overa C-18 Sep-Pak so that the product is trapped and residual acetonitrileis washed away with further water (10 mL). The product is then elutedinto the product vial with USP grade ethanol (0.5 mL) and diluted withsterile water (9.5 mL) providing a final formulation suitable forinjection.

Purity is determined by analytical HPLC equipped with a radioactivitydetector and identity is confirmed by comparison with HPLC data for thecorresponding unlabeled reference standard.

Synthesis of AD-C-002P-WZ01029

To dihydroxy coumarin (254 mg, 1 mmol) in 4 mL of NMP was added Cs₂CO₃(326 mg, 1 mmol) and ethylazido tosylate (241 mg, 1 mmol). The mixturewas stirred at rt for 15 h and diluted with Et₂O (50 mL). It was washedwith 1 M HCl (50 mL) and water (2×50 mL), dried over MgSO₄ andconcentrated. The crude product was purified with silica chromatography(DCM in hexane from 80% to 100%) to afford the desired mono-alkylatedproduct (72 mg) as an off-white solid.

¹H NMR (400 MHz, CDCl₃) δ 7.53-7.50 (m, 3H), 7.45-7.43 (m, 2H), 7.00 (d,J=8.8 Hz, 1H), 6.82 (d, J=8.8 Hz, 1H), 6.26 (s, 1H), 5.92 (s, 1H), 4.31(t, J=5.0 Hz, 2H), 3.72 (t, J=5.0 Hz, 2H); MS (ESI) m/z 324 (MAT).

Synthesis of AD-C-002S-WZ01035

To azidoethyl coumarin (42 mg, 0.13 mmol) in 1 mL of methanol was addedCuSO₄ (21 mg, 0.13 mmol), sodium ascorbate (28 mg, 0.13 mmol), andfluoropentyne (16.3 mg, 0.19 mmol). The reaction mixture was vigorouslystirred for 1 h and diluted with EtOAc (30 mL). It was washed with water(2×50 mL), dried over MgSO₄ and concentrated. The crude product waspurified with silica chromatography (eluted with 5% EtOAc in hexane to60%) to afford the desired compound (42 mg).

¹H NMR (400 MHz, CDCl₃/CD₃OD) δ 7.95 (s, 1H), 7.54-7.52 (m, 3H),7.48-7.44 (m, 2 H), 6.94 (d, J=8.8 Hz, 1H), 6.86 (d, J=8.8 Hz, 1H), 4.86(t, J=4.8 Hz, 2H), 4.55-4.51 (m, 3 H), 4.41 (t, J=6.0 Hz, 1H), 2.83 (t,J=7.2 Hz, 2H), 2.14-2.02 (m, 2H); MS (ESI) m/z 410 (M+H⁺).

Synthesis of 18F-Labeled AD-C-002S-WZ-01035 Preparation of [¹⁸F]5-Fluoro-pent-1-yne

[¹⁸F]Fluoride (600-900 mCi) as an enriched solution in H₂ ¹⁸O wasdelivered to the synthesis module. The [¹⁸F]fluoride was trapped on anion-exchange column and then eluted into the reaction vessel usingaqueous potassium carbonate (3.0 mg in 0.4 mL H₂O). Kryptofix-2.2.2phase transfer reagent was added (20.0 mg in 1.0 mL MeCN) and thewater-acetonitrile azeotrope was evaporated to dryness.Toluene-4-sulfonic acid pent-4-ynyl ester (20 mg in 0.8 mL MeCN) wasadded to the reactor and then the fluorination reaction was heated at110° C. for 5 min. Following fluorination, the crude reaction mixturewas purified by distillation to yield [¹⁸F] 5-fluoro-pent-1-yne as asolution in acetonitrile (trapped at −78° C. due to the volatility ofthe product).

Preparation of Triazole:

A mixture of azide precursor (5 mg), sodium ascorbate (40 mg),tris-(benzyltriazolylmethyl)amine (TBTA, 25 mg) and aqueous coppersulfate solution (0.1 M, 0.25 mL) in DMF (0.4 mL) and water (0.1 mL) wasadded to the cooled pentyne solution described above. The reactionmixture was then warmed to rt and stirred for 30 min. After this time,the reaction was purified by semi-preparative HPLC. The peakcorresponding to the product was collected and simultaneously dilutedwith sterile water (10 mL). The resulting mixture was passed over a C-18Sep-Pak so that the product was trapped and residual acetonitrile waswashed away with further water (10 mL). The product was then eluted intothe product vial with USP grade ethanol (0.5 mL) and diluted withsterile water (9.5 mL) to provide a final formulation (19 mCi in 10 mL)suitable for injection (10% decay corrected yield, 100% radiochemicalpurity).

Purity was determined by analytical HPLC equipped with a radioactivitydetector and identity was confirmed by comparison with HPLC data for thecorresponding unlabeled reference standard.

Synthesis of AD-CB-002P-WZ01031

To hydroxycarbazole (92 mg, 0.5 mmol) in 2 mL of NMP was added Cs₂CO₃(163 mg, 0.5 mmol) and ethylazido tosylate (121 mg, 0.5 mmol). Themixture was stirred at rt for 15 h and diluted with Et₂O (50 mL). It waswashed with 0.5 M HCl (50 mL) and water (2×50 mL), dried over MgSO₄ andconcentrated. The crude product was purified with silica chromatography(80% DCM in hexane to 100% DCM) to afford the desired product (76 mg) asa white solid.

¹H NMR (400 MHz, CDCl₃/acetone-d6) δ 9.98 (s, 1H), 7.95 (m, 2H), 7.41(d, J=8.4 Hz, 1H), 7.29 (t, J=8.0 Hz, 1H), 7.14 (t, J=8.0 Hz, 1H),);7.01 (s, 1H), 6.84 (d, J=8.4 Hz, 1 H), 4.28 (t, J=4.8 Hz, 2H), 3.67 (t,J=4.8 Hz, 2H); MS (ESI) m/z 253 (M+H⁺).

Synthesis of AD-CB-002S-WZ01033

To ethylazido carbazole (32 mg, 0.127 mmol) in 0.5 mL of DMF was addedCuI (7.6 mg, 0.04 mmol), DIPEA (16.4 mg, 0.127 mmol), and fluoropentyne(16.4 mg, 0.19 mmol). The reaction mixture was vigorously stirred for 1h and diluted with EtOAc (30 mL). It was washed with water (50 mL), 0.5M HCl (30 mL), water (2×50 mL), dried over MgSO₄ and concentrated. Thecrude product was pre-absorbed on silica (3 g) and loaded on a 4 gsilica column and eluted with 30% EtOAc in hexane to 50% to afford thedesired compound (20 mg).

¹H NMR (400 MHz, CDCl₃/CD₃OD) δ 7.95 (d, J=7.6 Hz, 1H), 7.91 (d, J=8.4Hz, 1H), 7.76 (s, 1H), 7.40 (d, J=8.0 Hz, 1H), 7.31 (t, J=7.6 Hz, 1H),7.14 (t, J=7.6 Hz, 1H); 6.94 (d, J=2.4 Hz, 1H), 6.78 (dd, J=8.8, 2.4 Hz,1H), 4.83-4.78 (m, 2H), 4.53-4.48 (m, 3H), 4.40 (t, J=6.0 Hz, 1H), 2.85(t, J=7.6 Hz, 2H), 2.10-1.99 (m, 2H); MS (ESI) m/z 339 (M+H⁺).

Synthesis of 18F-Labeled AD-CB-002S-WZ01033 Preparation of Triazole

A mixture of azide precursor (5 mg), sodium ascorbate (40 mg),tris-(benzyltriazolylmethyl)amine (TBTA, 25 mg) and aqueous coppersulfate solution (0.1 M, 0.25 mL) in DMF (0.4 mL) and water (0.1 mL) isadded to the cooled pentyne solution described above. The reactionmixture is then warmed to rt and stirs for 30 min. After this time, thereaction is purified by semi-preparative HPLC. The peak corresponding tothe product is collected and simultaneously diluted with sterile water(10 mL). The resulting mixture is passed over a C-18 Sep-Pak andresidual acetonitrile is washed away with additional water (10 mL). Theproduct is eluted into the product vial with USP grade ethanol (0.5 mL)and diluted with sterile water (9.5 mL) providing a final formulationsuitable for injection.

Purity is determined by analytical HPLC equipped with a radioactivitydetector and identity is confirmed by comparison with HPLC data for thecorresponding unlabeled reference standard.

Synthesis of AD-C-WZ01011

To dihydroxy coumarin (100 mg, 0.4 mmol) in 2.5 mL of NMP was addedCs₂CO₃ (130 mg, 0.4 mmol) and bromofluoroethane (46 mg, 0.36 mmol). Themixture was stirred at rt for 18 h and diluted with Et₂O (50 mL). It waswashed with 1 M HCl (50 mL) and water (2×50 mL) and dried over MgSO₄ andconcentrated. The crude product was purified with silica chromatography(MeOH in DCM from 0% to 1%) to afford the desired mono-alkylated product(25 mg) as a white solid.

¹H NMR (400 MHz, CDCl₃/CD₃OD) δ 7.55-7.48 (m, 5H), 6.96 (q, J=7.6 Hz,2H), 6.19 (s, 1H), 4.86 (m, 1H), 4.75 (m, 1H), 4.43 (m, 1H), 4.37 (m,1H); MS (ESI) m/z 301 (M+H⁺).

General Procedure for Carbazole N-Boc Protection:

To a round bottomed flask equipped with a magnetic stir bar, rubberseptum, and argon inlet containing THF (40 vol) was placed carbazole(1.0 equiv). To this solution was added NaH (60% dispersion in oil, 3equiv) at 0° C. and the reaction was allowed to stir at 0° C. for 30min. To this reaction was added (Boc)₂O (1.2 equiv) at 0° C. and thereaction was allowed to stir for 1 h. After the reaction was complete byLCMS, poured into water (25 vol) and extracted into EtOAc (3×20 vol).The combined organic extracts were washed with water (2×25 vol), dried(Na₂SO₄) and concentrated in vacuo. The residue was purified over silicagel using Hexanes:EtOAc as an eluent to afford the final product.

General Procedure for Carbazole N-Methylation:

To a round bottomed flask equipped with a magnetic stir bar, rubberseptum, and argon inlet containing THF (50 vol) was placed carbazole(1.0 equiv). To this solution was added NaH (60% dispersion in oil, 3equiv) at 0° C. and the reaction was allowed to stir at 0° C. for 30min. To this reaction was added MeOTf (1.0 equiv) at 0° C. and thereaction was allowed to stir for 1 h. After the reaction was complete byLCMS, poured into water (25 vol) and extracted into EtOAc (3×20 vol).The combined organic extracts were washed with water (2×25 vol), dried(Na₂SO₄) and concentrated in vacuo. The residue was purified over silicagel using Hexanes:EtOAc as an eluent to afford the final product.

General Experimental Procedure for Phenolic Alkylation:

To a round bottomed flask equipped with a magnetic stir bar containingDMF (20 vol) was placed phenol (1 equiv). To this solution was addedalkylating agent (1.0 equiv), Cs₂CO₃ (1.2 equiv) and the reaction wasallowed to stir at 60° C. for 16 h. The reaction was then poured intowater (25 vol) and extracted into EtOAc (3×20 vol). The combined organicextracts were washed with water (2×25 vol), dried (Na₂SO₄) andconcentrated in vacuo. The residue was purified over silica gel usingHexanes:EtOAc as an eluent to afford the final product.

General Experimental Procedure for Suzuki Coupling Reaction:

To a round bottomed flask equipped with a magnetic stir bar rubberseptum, and argon inlet containing toluene:H₂O (1:1, 40 vol) was placedchloro compound (1 equiv). To this solution was added boronic acid (1.5equiv), Pd(PPh₃)₄ (0.02 equiv), K₂CO₃ and the reaction was allowed tostir at 110° C. for 16 h. The reaction was then poured into water (25vol) and extracted into EtOAc (3×20 vol). The combined organic extractswere washed with water (2×25 vol), dried (Na₂SO₄) and concentrated invacuo. The residue was purified over silica gel using Hexanes:EtOAc asan eluent to afford the final product.

General Experimental Procedure for Carbazole Formation Using P(OEt)₃:

To a round bottomed flask equipped with a magnetic stir bar containingP(OEt)₃ (25 vol) was placed biaryl (1 equiv). The reaction was allowedto stir at 150° C. for 16 h. After the reaction was complete, P(OEt)₃was removed in vacuo. The residue was purified over silica gel usingHexanes:EtOAc as the eluent to afford the final compound.

Synthesis of CB1-Nosylate Precursor:

Preparation of ethane-1,2-diyl bis(2-nitrobenzenesulfonate) (DHK-4-14)

To a 50 mL round bottomed flask equipped with a magnetic stir barcontaining DCM (10 mL) was placed 1,2-ethanediol (0.25 g, 4.0 mmol). Tothis solution was added nosyl chloride (1.9 g, 8.5 mmol) and Et₃N (0.90g, 8.9 mmol) at 0° C. and the reaction was allowed to stir at roomtemperature for 16 h. After the reaction was complete, the white solidwas filtered, washed with DCM (100 mL) and dried in vacuo to affordDHK-4-14 (1.3 g, 75%) as a colorless solid. MS: [M+Na]⁺: 455.0

Preparation of 2-(9H-carbazol-2-yloxy)ethyl 2-nitrobenzenesulfonate(DHK-4-15)

To a 25 mL round bottomed flask equipped with a magnetic stir barcontaining DMF (5 vol) was placed carbazole (0.2 g, 1.1 mmol). To thissolution was added the DHK-4-14 (0.52 g, 1.2 mmol), Cs₂CO₃ (0.43 g, 1.3mmol) and the reaction was allowed to stir at room temperature for 16 h.The reaction was then poured into water (25 mL) and extracted into EtOAc(4×50 mL). The combined organic extracts were dried (Na₂SO₄) andconcentrated in vacuo. The crude residue was purified by flashchromatography using Hexanes:EtOAc (50:50) on a Combiflash purificationsystem to yield DHK-4-15 as a white solid (0.28 g, 62%). MS: [M+Na]⁺:435.0

Synthesis of CB-5:

Preparation of tert-butyl2-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-9H-carbazole-9-carboxylate: CB-5:DHK-4-27

General experimental procedure for carbazole N-Boc protection wasfollowed. Reaction was performed on a 0.03 g scale. Product eluted outin 30-35% EtOAc:Hexanes mixture in a gradient elution on a Combiflashpurification system. Isolated 0.03 g (74%) of CB-5 as a colorless oil.MS: [M+H]⁺: 418.0

Synthesis of CB-6: DHK-4-28

Preparation of2-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-9-methyl-9H-carbazole: CB-6

General experimental procedure for carbazole N-methylation was followed.Reaction was performed on a 0.05 g scale. Product eluted out in 40-45%EtOAc:Hexanes mixture in a gradient elution on a Combiflash purificationsystem. Isolated 0.04 g (78%) of CB-6 as a white solid. MS: [M+H]⁺:332.1.

Synthesis of N-Boc-Protected CB-3 Precursor:

Preparation of tert-butyl2-(2-(2-(2-(tosyloxy)ethoxy)ethoxy)ethoxy)-9H-carbazole-9-carboxylate:DHK-4-32

General experimental procedure for carbazole N-Boc protection wasfollowed. Reaction was performed on a 0.07 g scale. Product eluted outin 40% EtOAc:Hexanes mixture in a gradient elution on a Combiflashpurification system. Isolated 0.07 g (82%) of DHK-4-32 as white solid.MS: [M+Na]⁺: 592.

Synthesis of N-methyl CB-3 Precursor:

Preparation of 2-(2-(2-(9-methyl-9H-carbazol-2-yloxy)ethoxy)ethoxy)ethyl4-methylbenzenesulfonate: DHK-4-30

General experimental procedure for carbazole N-methylation was followed.Reaction was performed on a 0.075 g scale. Product eluted out in 40%EtOAc:Hexanes mixture in a gradient elution on a Combiflash purificationsystem. Isolated 0.07 g (91%) of DHK-4-30 as a white solid. MS: [M+H]⁺:484.2

Synthesis of CB-7 Std:

Preparation of1-chloro-4-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-2-nitrobenzene: DHK-4-51

General experimental procedure for phenolic alkylation was followed.Reaction was performed on a 0.25 g scale. Product eluted out in 20-30%EtOAc:Hexanes mixture in a gradient elution on a Combiflash purificationsystem. Isolated 0.44 g (99%) of DHK-4-51 as yellow oil. MS: [M+H]⁺:308.0.

Preparation of4′-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-N,N-dimethyl-2′-nitrobiphenyl-4-amine:DHK-4-26

General experimental procedure for Suzuki coupling reaction wasfollowed. Reaction was performed on a 0.11 g scale. Product eluted outin 50-60% EtOAc:Hexanes mixture in a gradient elution on a Combiflashpurification system. Isolated 0.06 g (43%) of DHK-4-26 as yellow oil.MS: [M+H]⁺: 393.1

Preparation of7-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-N,N-dimethyl-9H-carbazol-2-amine:DHK-4-29: CB-7

General experimental procedure for carbazole formation using P(OEt)₃ wasfollowed. Reaction was performed on a 0.06 g scale. Product eluted outin 70-80% EtOAc:Hexanes mixture in a gradient elution on a Combiflashpurification system. Isolated 0.03 g (49%) of DHK-4-29 CB-7 as whitesolid. MS: [M+H]⁺: 361.1.

Synthesis of CB-9 Std:

Preparation of1-chloro-4-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-2-nitrobenzene: DHK-4-51

General experimental procedure for phenolic alkylation was followed.Reaction was performed on a 0.25 g scale. Product eluted out in 20-30%EtOAc:Hexanes mixture in a gradient elution on a Combiflash purificationsystem. Isolated 0.44 g (99%) of DHK-4-51 as yellow oil. MS: [M+H]⁺:308.0.

Preparation ofN-(4′-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-2′-nitrobiphenyl-4-yl)acetamide:DHK-4-31

General experimental procedure for Suzuki coupling reaction wasfollowed. Reaction was performed on a 0.11 g scale. Product eluted outin 80-90% EtOAc:Hexanes mixture in a gradient elution on a Combiflashpurification system. Isolated 0.14 g (100%) of DHK-4-31 as yellow oil.MS: [M+H]⁺: 407.0.

Preparation ofN-(7-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-9H-carbazol-2-yl)acetamide:DHK-4-33: CB-9

General experimental procedure for carbazole formation using P(OEt)₃ wasfollowed. Reaction was performed on a 0.15 g scale. Product eluted outin 90% EtOAc:Hexanes mixture in a gradient elution on a Combiflashpurification system. Isolated 0.03 g (49%) of CB-9 as white solid. MS:[M+H]⁺: 375.1.

Synthesis of CB-28 Std:

Preparation of1-chloro-4-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-2-nitrobenzene: DHK-4-51

General experimental procedure for phenolic alkylation was followed.Reaction was performed on a 0.25 g scale. Product eluted out in 20-30%EtOAc:Hexanes mixture in a gradient elution on a Combiflash purificationsystem. Isolated 0.44 g (99%) of DHK-4-51 as yellow oil. MS: [M+H]⁺:308.0.

Preparation of3-(4-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-2-nitrophenyl)pyridine:DHK-4-56

General experimental procedure for Suzuki coupling reaction wasfollowed. Reaction was performed on a 0.095 g scale. Product eluted outin 40-50% EtOAc:Hexanes mixture in a gradient elution on a Combiflashpurification system. Isolated 0.01 g (9%) of DHK-4-56 as yellow oil. MS:[M+H]⁺: 351.1.

Preparation of7-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-9H-pyrido[2,3-b]indole DHK-4-58:CB-28

General experimental procedure for carbazole formation using P(OEt)₃ wasfollowed. Reaction was performed on a 0.01 g scale. Product eluted outin 50% EtOAc:Hexanes mixture in a gradient elution on a Combiflashpurification system. Isolated 0.002 g (22%) of CB-28 as white solid. MS:[M+H]⁺: 319

Synthesis of CB-7-Precursor

Preparation of 4-(benzyloxy)-1-chloro-2-nitrobenzene: DHK-4-63

General experimental procedure for phenolic alkylation was followed.Reaction was performed on a 1 g scale. K₂CO₃ was used as a base andacetone was used as the solvent. Reaction time was 4 h. Product elutedout in 20-30% EtOAc:Hexanes mixture in a gradient elution on aCombiflash purification system. Isolated 1.45 g (95%) of DHK-4-63 aswhite crystalline solid. MS: [M+H]⁺: 264.0

Preparation of 3 4′-(benzyloxy)-N,N-dimethyl-2′-nitrobiphenyl-4-amine:DHK-4-66

General experimental procedure for Suzuki coupling reaction wasfollowed. Reaction was performed on a 0.47 g scale. Product eluted outin 20-30% EtOAc:Hexanes mixture in a gradient elution on a Combiflashpurification system. Isolated 0.21 g (34%) of DHK-4-66 as orange solid.MS: [M+H]⁺: 349.1

Preparation of 7-(benzyloxy)-N,N-dimethyl-9H-carbazol-2-amine DHK-4-68

General experimental procedure for carbazole formation using P(OEt)₃ wasfollowed. Reaction was performed on a 0.21 g scale. Product eluted outin 20-30% EtOAc:Hexanes mixture in a gradient elution on a Combiflashpurification system. Isolated 0.13 g (68%) of DHK-4-68 as white solid.MS: [M+H]⁺: 317.1

Preparation of tert-butyl2-(benzyloxy)-7-(dimethylamino)-9H-carbazole-9-carboxylate: DHK-4-69

General experimental procedure for carbazole N-Boc protection wasfollowed. Reaction was performed on a 0.13 g scale. Reaction temperaturewas carried at room temperature for 16 h. Product eluted out in 10%EtOAc:Hexanes mixture in a gradient elution on a Combiflash purificationsystem. Isolated 0.12 g (70%) of DHK-4-69 as white solid. MS: [M+H]⁺:417:2.

Preparation of tert-butyl2-(dimethylamino)-7-hydroxy-9H-carbazole-9-carboxylate: DHK-4-71

To a 50 mL round bottomed flask equipped with a magnetic stir barcontaining EtOAc (50 mL) was placed DHK-4-69 (0.11 g, 0.19 mmol). Tothis solution was added Pd/C (10%, 20 mg) and the reaction was allowedto stir under H₂ (1 atm) at RT for 16 h. After the reaction wascomplete, the reaction mixture was filtered through celite and thevolatiles were removed in vacuo to afford DHK-4-71 (0.09 g, 100%) aswhite solid.

Preparation of tert-butyl2-(dimethylamino)-7-(2-(2-(2-(tosyloxy)ethoxy)ethoxy)ethoxy)-9H-carbazole-9-carboxylate:DHK-4-72: CB-7 precursor:

General experimental procedure for phenolic alkylation was followed.Reaction was performed on a 0.09 g scale. Product eluted out in 45%EtOAc:Hexanes mixture in a gradient elution on a Combiflash purificationsystem. Isolated 0.07 g (41%) of CB-7 precursor as white solid. MS:[M+H]⁺: 613.2.

Synthesis of AD-CB-003S-WZ0129

To2,2′-(ethane-1,2-diylbis(oxy))bis(ethane-2,1-diyl)bis(4-methylbenzenesulfonate)(8.7 g, 19 mmol) was added TBAF (22.8 mL, 1.0 M THF solution, 22.8mmol). The mixture was heated to reflux for 1 h under Ar atmosphere andcooled to rt and concentrated under reduced pressure. The crude materialwas purified with silica chromatography (5% to 40% THF in hexane) toafford 2-(2-(2-fluoroethoxy)ethoxy)ethyl 4-methylbenzenesulfonate as aclear oil (2.5 g, 43%). ¹H NMR (400 MHz, CDCl₃) δ 7.80 (d, J=8.4 Hz,2H), 7.34 (d, J=8.4 Hz, 2H), 4.61 (m, 1H), 4.49 (m, 1H), 4.16 (m, 2H),3.75 (m, 1H), 3.71-3.67 (m, 3H), 3.62 (m, 4H); MS (ESI) m/z 307 (M+H⁺).

To 2-hydroxycarbazole (45 mg, 0.25 mmol) and2-(2-(2-fluoroethoxy)ethoxy)ethyl 4-methylbenzenesulfonate (82 mg, 0.27mmol) in 0.5 mL NMP was added Cs₂CO₃ (82 mg, 0.25 mmol). The mixture wasstirred at rt for 15 h under Ar atmosphere and diluted with Et₂O (50mL). It was washed with water (3×50 mL) and dried over MgSO₄. Solventwas removed under reduced pressure and the crude product was purifiedwith silica chromatography (5% to 50% EtOAc in hexane) to afford thedesired product as white solid (37 mg, 47%). ¹H NMR (400 MHz, CDCl₃) δ8.02 (s, 1H), 7.96 (d, J=7.2 Hz, 1H), 7.91 (d, J=8.4 Hz, 1H), 7.38-7.33(m, 2H), 7.20 (m, 1H), 6.91 (d, J=2.4 Hz, 1H), 6.86 (dd, J=8.8, 2.4 Hz,1H), 4.63 (m, 1H), 4.51 (m, 1 H), 4.21 (m, 2H), 3.90 (m, 2H), 3.80-3.76(m, 3H), 3.74-3.71 (m, 3H); MS (ESI) m/z 318 (M+H⁺).

Synthesis of AD-CB-003P-WZ0141

To 2-hydroxycarbazole (183 mg, 1 mmol) and2-(2-(2-fluoroethoxy)ethoxy)ethyl 4-methylbenzenesulfonate (687 mg, 1.5mmol) in 5 mL NMP was added Cs₂CO₃ (326 mg, 1 mmol). The mixture wasstirred at rt for 15 h under Ar atmosphere and diluted with Et₂O (100mL). It was washed with water (3×100 mL) and dried over MgSO₄. Solventwas removed under reduced pressure and the crude product was purifiedwith silica chromatography (5% to 60% EtOAc in hexane) to afford thedesired product as white solid (165 mg, 35%). NMR (400 MHz, CDCl3) 8.21(s, 1H), 7.95 (d, J=7.2 Hz, 1H), 7.91 (d, J=8.4 Hz, 1H), 7.77-7.75 (m,2H), 7.37-7.30 (m, 2H), 7.28 (s, 1H), 7.25 (m, 1H), (td, J=7.6, 1.2 Hz,1H), 6.92 (d, J=2.4 Hz, 1H), 6.83 (dd, J=8.8, 2.4 Hz, 1H), 4.15 (m, 4H),3.84 (m, 2H), 3.69-3.65 (m, 4H), 3.62-3.59 (m, 2H), 2.38 (s, 3H); MS(ESI) m/z 470 (MAT), 492 (M+Na⁺).

AD-CB-004S-WZ01165

To 4-chloro-3-nitrophenol (1.74 g, 10 mmol) and benzyl bromide (2.05 g,12 mmol) in 25 mL of acetone was added K₂CO₃ (2.76 g, 20 mmol). Themixture was heated at 60° C. for 4 h under Ar atmosphere and cooled tort. It was filtered and the solid was washed with ether (80 mL) and thecombined filtrate was concentrated and chromatographed (EtOAc in hexane,3% to 30% gradient) to afford 4-(benzyloxy)-1-chloro-2-nitrobenzene as alight-yellow solid (2.5 g, 95%). ¹H NMR (400 MHz, CDCl₃) δ 7.46 (d,J=2.8 Hz, 1H), 7.42-7.34 (m, 5H), 7.11 (dd, J=8.8, 2.8 Hz, 1H), 5.08 (s,2H); MS (ESI) m/z 264 (MAI).

To 4-(benzyloxy)-1-chloro-2-nitrobenzene (526 mg, 2 mmol) and tert-butyl4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate (670 mg,2.1 mmol) in 12 mL dioxane was added 4 mL of a 1 M Na₂CO₃ (aq) solutionand Tetrakis(triphenylphosphine)palladium (69 mg, 0.06 mmol). Thesuspension was heated at reflux for 15 h under Ar atmosphere and cooledto rt. It was added EtOAc (100 mL) and washed with brine (80 mL), water(80 mL), and dried over MgSO₄. After solvent removal, the residue waschromatographed (hexane/EtOAc) to afford tert-butyl4′-(benzyloxy)-2′-nitrobiphenyl-4-ylcarbamate as a yellow solid (740 mg,88%). ¹H NMR (400 MHz, CDCl₃) δ 7.44-7.34 (m, 8H), (d, J=8.4 Hz, 1H),7.20-7.16 (m, 3H), 6.50 (s, 1H), 5.12 (s, 2H), 1.51 (s, 9H); MS (ESI)m/z 443 (M+Na⁺).

A suspension of tert-butyl 4′-(benzyloxy)-2′-nitrobiphenyl-4-ylcarbamate(740 mg, 1.67 mmol) in 2 mL of triethyl phosphite was heated at 145° C.for 15 h under Ar atmosphere and cooled to rt. It was added 10 mL ofhexane and let sit for 10 min. Solid was collected via filtration andwashed with ether/hexane (v:v 1/1, 10 mL) and dried under high vacuum toafford tert-butyl 7-(benzyloxy)-9H-carbazol-2-ylcarbamate as a off-whitesolid (480 mg, 74%). ¹H NMR (400 MHz, CDCl₃) δ 7.89 (s, 1H), 7.83-7.78(m, 3H), 7.46 (d, J=7.2 Hz, 2H), 7.38 (m, 2H), 7.32 (d, J=7.2 Hz, 1H),6.94 (d, J=2.0 Hz, 1H), 6.88 (dd, J=8.8, 2.4 Hz, 1H), 6.83 (dd, J=8.4,2.0 Hz, 1H), 6.60 (s, 1H), 5.15 (s, 2H), 1.52 (s, 9H); MS (ESI) m/z 389(M+H⁺).

To tert-butyl 7-(benzyloxy)-9H-carbazol-2-ylcarbamate (220 mg, 0.56mmol) in 50 mL MeOH was added Palladium on activated carbon (80 mg). Themixture was stirred at rt under H2 atmosphere for 3 h. Solid wasfiltered off and the filtrate was concentrated to afford tert-butyl7-hydroxy-9H-carbazol-2-ylcarbamate as a brown solid (165 mg, 100%).This material was used directly for the next reaction withoutpurification. MS (ESI) m/z 619 (2M+Na⁺).

To tert-butyl 7-hydroxy-9H-carbazol-2-ylcarbamate (165 mg, 0.55 mmol)and 2-(2-(2-fluoroethoxy)ethoxy)ethyl 4-methylbenzenesulfonate (202 mg,0.66 mmol) in 2 mL of NMP was added Cs₂CO₃ (179 mg, 0.55 mmol). Themixture was stirred at rt for 15 h under Ar atmosphere and diluted withEtOAc (50 mL). It was washed with water (3×50 mL) and dried over MgSO₄.After solvent removal, the residue was chromatographed (hexane/EtOAc) toafford tert-butyl7-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-9H-carbazol-2-ylcarbamate as awhite solid (130 mg, 55%). ¹H NMR (400 MHz, CDCl₃) δ 7.94 (s, 1H),7.83-7.79 (m, 3H), 6.91 (d, J=2.0 Hz, 1H), 6.86 (dd, J=8.4, 2.0 Hz, 1H),6.83 (dd, J=8.8, 2.4 Hz, 1H), 6.63 (s, 1H), 4.64 (m, 1H), 4.51 (m, 1 H),4.21 (m, 2H), 3.91 (m, 2H), 3.81-3.71 (m, 6H), 1.55 (s, 9H); MS (ESI)m/z 433 (M+H⁺).

To tert-butyl7-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-9H-carbazol-2-ylcarbamate (130mg, 0.3 mmol) was added 10 mL of a 4 M HCl in dioxane solution. Themixture was stirred at rt for 5 h and concentrated under reducedpressure. The residue was washed with ether (15 mL) and suspended inEtOAc (50 mL). To this suspension was added 10 mL of a NaHCO₃ (sat.) andthe mixture was stirred for 5 min. The organic layer was dried overMgSO₄ and concentrated to afford7-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-9H-carbazol-2-amine as a brownsolid (95 mg, 95%). MS (ESI) m/z 333 (M+H⁺).

A mixture of 7-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-9H-carbazol-2-amine(95 mg, 0.28 mmol), paraformaldehyde (43 mg, 1.43 mmol), and NaOMe (492mg, 25% MeOH solution, 2.3 mmol) in 8 mL of MeOH was heated at refluxfor 1.5 h under Ar atmosphere and cooled to rt. To this mixture wasadded NaBH₄ (54 mg, 1.43 mmol) and the mixture was heated at reflux for2 h. After cooling to rt, the mixture was quenched onto ice. It wasextracted with ether (3×30 mL) and the combined organic phase was driedover MgSO₄ and concentrated. The crude product was purified withchromatography (hexane/EtOAc) to afford7-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-N-methyl-9H-carbazol-2-amine(AD-CB-003P-WZ0141) as a light-brown solid (55 mg, 56%).

¹H NMR (400 MHz, CDCl₃) δ 7.76 (s, 1H), 7.77 (t, J=8.8 Hz, 2H), 6.78(dd, J=8.0, 2.0 Hz, 1 H), 6.77 (s, 1H), 6.53 (dd, J=8.4, 2.0 Hz, 1H),6.46 (s, 1H), 4.62 9m, 1H), 4.50 (m, 1H), 4.13 (t, J=5.2 Hz, 2H), 3.85(t, J=5.2 Hz, 2H), 3.83 (s, 1H), 3.79-3.67 (m, 6H), 2.87 (s, 3H); MS(ESI) m/z 347 (M+H⁺).

AD-CB-004 Pa-WZ01179

To tert-butyl 7-(benzyloxy)-9H-carbazol-2-ylcarbamate (200 mg, 0.51mmol) was added 10 mL of a 4 M HCl in dioxane solution. The mixture wasstirred at rt for 4 h and concentrated under reduced pressure. Theresidue was washed with ether (15 mL) and suspended in EtOAc (50 mL). Tothis suspension was added 10 mL of a NaHCO₃ (sat.) and the mixture wasstirred for 5 min. The organic layer was dried over MgSO₄ andconcentrated to afford 7-(benzyloxy)-9H-carbazol-2-amine as a brownsolid (150 mg, 100%). ¹H NMR (400 MHz, DMSO-d6) δ 11.33 (s, 1H), 7.99(d, J=8.4 Hz, 1H), 7.92 (d, J=8.8 Hz, 1H), 7.42 (d, J=6.8 Hz, 2H),7.34-7.21 (m, 3H), 7.27-7.23 (m, 1H), 7.00-6.97 (m, 2H), 6.81 (dd,J=8.8, 2.4 Hz, 1 H), 5.12 (s, 2H); MS (ESI) m/z 289 (M+H⁺).

A mixture of 7-(benzyloxy)-9H-carbazol-2-amine (150 mg, 0.52 mmol),paraformaldehyde (78 mg, 2.6 mmol), and NaOMe (900 mg, 25% MeOHsolution, 4.16 mmol) in 15 mL of MeOH was heated at reflux for 2 h underAr atmosphere and cooled to rt. To this mixture was added NaBH₄ (98 mg,2.6 mmol) and the mixture was heated at reflux for 2 h. After cooling tort, the mixture was quenched onto ice (30 g). It was extracted withEtOAc (3×50 mL) and the combined organic phase was dried over MgSO₄ andconcentrated. The crude product was purified with chromatography(hexane/EtOAc) to afford 7-(benzyloxy)-N-methyl-9H-carbazol-2-amine as alight-brown solid (130 mg, 82%). ¹H NMR (400 MHz, acetone-d6) δ 9.78 (s,1H), 7.72 (d, J=8.4 Hz, 1H), 7.66 (d, J=8.8 Hz, 1H), 7.49 (d, J=7.2 Hz,2H), 7.37 (m, 2H), 7.32-7.28 (m, 1H), 6.98 (d, J=2.4 Hz, 1H), 6.78 (dd,J=8.4, 2.4 Hz, 1H), 6.56 (d, J=2.0 Hz, 1H), 6.49 (dd, J=8.4, 2.4 Hz,1H), 5.13 (s, 2H), 4.96 (s, 1H), 2.82 (s, 3H); MS (ESI) m/z 303 (M+H⁺).

To 7-(benzyloxy)-N-methyl-9H-carbazol-2-amine (120 mg, 0.4 mmol), formicacid (55 mg, 1.2 mmol) and DMAP (5 mg, 0.04 mmol) in 3 mL of pyridinewas added portionwise EDC (230 mg, 1.2 mmol). The mixture was stirred atrt for 3 h under Ar atmosphere and concentrated under reduced pressure.The residue was diluted with EtOAc (50 mL) and washed with water (2×50mL), 0.5 M HCl(2×50 mL), and brine (50 mL), and dried over MgSO₄. Aftersolvent removal, the crude product was purified with chromatography(hexane/EtOAc) to affordN-(7-(benzyloxy)-9H-carbazol-2-yl)-N-methylformamide as a white solid(110 mg, 83%). ¹H NMR (400 MHz, acetone-d6) δ 10.34 (s, 1H), 8.49 (s,1H), 8.02 (d, J=8.4 Hz, 1H), 7.98 (d, J=8.8 Hz, 1H), 7.51 (d, J=7.2 Hz,2H), 7.39 (m, 2H), 7.34-7.28 (m, 1H), 7.13 (d, J=2.4 Hz, 1H), 7.08 (dd,J=8.4, 2.4 Hz, 1H), 6.91 (dd, J=8.4, 2.4 Hz, 1H), 5.19 (s, 2H), 3.31 (s,3H); MS (ESI) m/z 331 (MAT).

To N-(7-(benzyloxy)-9H-carbazol-2-yl)-N-methylformamide (110 mg, 0.33mmol) in 50 mL MeOH was added Palladium on activated carbon (50 mg). Themixture was stirred at rt under H2 atmosphere for 15 h. Solid wasfiltered off and the filtrate was concentrated to affordN-(7-hydroxy-9H-carbazol-2-yl)-N-methylformamide as a brown solid (75mg, 94%). This material was used directly for the next reaction withoutpurification. MS (ESI) m/z 241 (M+H⁺).

To N-(7-hydroxy-9H-carbazol-2-yl)-N-methylformamide (45 mg, 0.187 mmol)and 2-(2-(2-fluoroethoxy)ethoxy)ethyl 4-methylbenzenesulfonate (172 mg,0.38 mmol) in 0.5 mL NMP was added Cs₂CO₃ (65 mg, 0.2 mmol). The mixturewas stirred at rt for 15 h under Ar atmosphere and diluted with EtOAc(50 mL). It was washed with water (2×50 mL), 0.5 M HCl (50 mL) and brine(50 mL), and dried over MgSO₄. Solvent was removed under reducedpressure and the crude product was purified with silica chromatography(hexane/EtOAc) to afford2-(2-(2-(7-(N-methylformamido)-9H-carbazol-2-yloxy)ethoxy)ethoxy)ethyl4-methylbenzenesulfonate (AD-CB-004 Pa-WZ01179) as a light-brown oil (48mg, 48%). ¹H NMR (400 MHz, CDCl₃) δ 8.52 (s, 1 H), 8.45 (s, 1H), 7.95(d, J=8.4 Hz, 1H), 7.90 (d, J=8.8 Hz, 1H), 7.80-7.77 (m, 2H), 7.30 (d,J=8.0 Hz, 2H), 7.17 (d, J=2.4 Hz, 1H), 7.02 (d, J=2.0 Hz, 1H), 7.01 (dd,J=8.0, 2.0 Hz, 1H), 6.89 (dd, J=8.8, 2.4 Hz, 1H), 4.23 (m, 1H), 4.17 (m,2H), 3.88 (m, 2H), 3.72-3.68 (m, 4H), 3.66-3.61 (m, 2H), 3.39 (s, 3H),2.41 (s, 3H); MS (ESI) m/z 527 (M+H⁺).

AD-CB-004Pb-WZ01191

To N-(7-(benzyloxy)-9H-carbazol-2-yl)-N-methylformamide (140 mg, 0.42mmol) in 5 mL dry THF at 0° C. under Ar atmosphere was added NaH (50 mg,60% in oil, 1.26 mmol) in 4 portions. The mixture was then stirred at rtfor 20 min followed by the addition of tert-butyl phenyl carbonate (244mg, 1.26 mmol) with a syringe. The reaction was allowed to stir at rtfor 3 h and quenched onto ice (30 g). The mixture was extracted withEtOAc (2×40 mL) and the combined organic phase was dried over MgSO₄.After solvent removal, the residue was chromatographed to affordtert-butyl2-(benzyloxy)-7-(N-methylformamido)-9H-carbazole-9-carboxylate as awhite solid (120 mg, 66%). ¹H NMR (400 MHz, CDCl₃) δ 8.56 (s, 1H), 8.15(s, 1H), 7.98 (s, 1H), 7.86 (d, J=8.4 Hz, 1H), 7.83 (d, J=8.4 Hz, 1H),7.50-7.49 (m, 2H), 7.43-7.39 (m., 2H), 7.37-7.32 (m, 1H), 7.13 (dd,J=8.4, 2.0 Hz, 1H), 7.05 (dd, J=8.8, 2.4 Hz, 1H), 5.18 (s, 2H), 3.41 (s,3H), 1.75 (s, 9H); MS (ESI) m/z 431 (M+H⁺).

To tert-butyl2-(benzyloxy)-7-(N-methylformamido)-9H-carbazole-9-carboxylate (120 mg,0.28 mmol) in 50 mL MeOH was added Palladium on activated carbon (50mg). The mixture was stirred at rt under H2 atmosphere for 3 h. Solidwas filtered off and the filtrate was concentrated to afford tert-butyl2-hydroxy-7-(N-methylformamido)-9H-carbazole-9-carboxylate as a brownsolid (95 mg, 100%). This material was used directly for the nextreaction without purification. MS (ESI) m/z 341 (M+H⁺).

To tert-butyl 2-hydroxy-7-(N-methylformamido)-9H-carbazole-9-carboxylate(65 mg, 0.19 mmol) and 2-(2-(2-fluoroethoxy)ethoxy)ethyl4-methylbenzenesulfonate (174 mg, 0.38 mmol) in 0.5 mL NMP was addedCs₂CO₃ (68 mg, 0.21 mmol). The mixture was stirred at rt for 15 h underAr atmosphere and diluted with EtOAc (80 mL). It was washed with water(3×50 mL), and dried over MgSO₄. Solvent was removed under reducedpressure and the crude product was purified with silica chromatography(hexane/EtOAc) to afford tert-butyl2-(N-methylformamido)-7-(2-(2-(2-(tosyloxy)ethoxy)ethoxy)ethoxy)-9H-carbazole-9-carboxylate(AD-CB-004Pb-WZ01191) as a clear oil (75 mg, 63%). ¹H NMR (400 MHz,CDCl₃) δ 8.56 (s, 1H), 8.14 (s, 1H), 7.89 (s, 1H), 7.87 (d, J=8.0 Hz,1H), 7.83 (d, J=8.8 Hz, 1H), 7.79 (m, 2H), 7.32 (d, J=8.4 Hz, 2H), 7.15(dd, J=8.4, 2.0 Hz, 1H), 7.00 (dd, J=8.8, 2.4 Hz, 1H), 4.23 (m, 1H),3.89 (m, 2H), 3.88 (m, 2H), 3.73-3.68 (m, 4H), 3.66-3.63 (m, 2H), 3.41(s, 3H), 2.42 (s, 3H), 1.76 (s, 9H); MS (ESI) m/z 527 (M+H⁺).

AD-CB-010S-WZ01183

To 4-(benzyloxy)-1-chloro-2-nitrobenzene (394 mg, 1.5 mmol)N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)formamide (370mg, 1.5 mmol) in 6 mL dioxane was added 3 mL of a 1 M Na₂CO₃ (aq)solution and Tetrakis(triphenylphosphine)palladium (52 mg, 0.045 mmol).The suspension was headed at reflux for 15 h under Ar atmosphere andcooled to rt. It was added EtOAc (80 mL) and washed with brine (50 mL),water (2×80 mL), and dried over MgSO₄. After solvent removal, theresidue was chromatographed (hexane/EtOAc) to affordN-(4′-(benzyloxy)-2′-nitrobiphenyl-4-yl)formamide as a yellow solid (395mg, 75%). MS (ESI) m/z 349 (M+H⁺).

A suspension of N-(4′-(benzyloxy)-2′-nitrobiphenyl-4-yl)formamide (350mg, 1 mmol) in 2 mL of triethyl phosphite was heated at 145 C for 15 hunder Ar atmosphere and cooled to rt. It was added 10 mL of hexane andlet sit for 10 min. Solid was collected via filtration and washed withether/hexane (v:v 1/1, 10 mL) and dried under high vacuum toN-(7-(benzyloxy)-9H-carbazol-2-yl)formamide as a light-brown solid (280mg, 88%). MS (ESI) m/z 317 (M+H⁺).

To N-(7-(benzyloxy)-9H-carbazol-2-yl)formamide (250 mg, 0.79 mmol) in 50mL MeOH was added Palladium on activated carbon (60 mg). The mixture wasstirred at rt under H2 atmosphere for 15 h. The mixture was concentratedunder reduced pressure and dried under high vacuum to affordN-(7-hydroxy-9H-carbazol-2-yl)formamide mixed with the catalyst as ablack solid (240 mg). This material was used directly for the nextreaction without purification. MS (ESI) m/z 227 (M+H⁺).

To N-(7-hydroxy-9H-carbazol-2-yl)formamide (30 mg) and2-(2-(2-fluoroethoxy)ethoxy)ethyl 4-methylbenzenesulfonate (48 mg, 0.156mmol) in 0.3 mL of NMP was added Cs₂CO₃ (42 mg, 0.13 mmol). The mixturewas stirred at rt for 15 h under Ar atmosphere and diluted with EtOAc(30 mL). It was washed with water (3×30 mL) and dried over MgSO₄. Aftersolvent removal, the residue was chromatographed (hexane/EtOAc) toN-(7-(2-fluoroethoxy)-9H-carbazol-2-yl)formamide (AD-CB-010S-WZ01183) asa white solid (17 mg, 36%). For the major rotomer: ¹H NMR (400 MHz,acetone-d6) δ 10.10 (s, 1H), 9.28 (s, 1H), 8.39 (d, J=1.6 Hz, 1H), 8.11(d, J=2.0 Hz, 1H), 7.91 (s, 1H), 7.87 (d, J=8.4, Hz, 2H), 7.17 (dd,J=8.4, 2.0 Hz, 1H), 7.01 (d, J=2.0 Hz, 1H), 6.80 (dd, J=8.4, 2.0 Hz,1H), 4.58 (m, 1H), 4.46 (m, 1H), 4.21 (m, 2H), 3.88 (m, 2H), 3.77 (m,1H), 3.73-3.66 (m, 5H); MS (ESI) m/z 361 (M+H⁺).

AD-CB-012S-WZ01185

Compound AD-CB-012S-WZ01185 was prepared using the same procedure forthe preparation of AD-CB-010S-WZ01183. For the major rotomer: ¹H NMR(400 MHz, acetone-d6) δ 10.08 (s, 1H), 9.19 (s, 1H), 8.26 (d, J=1.6 Hz,1H), 8.00 (d, J=2.0 Hz, 1H), 7.84-7.77 (m, 3H), 7.07 (dd, J=8.4, 2.0 Hz,1H), 6.93 (d, J=2.0 Hz, 1H), 6.69 (dd, J=8.4, 2.0 Hz, 1H), 4.73 (m, 1H),4.61 (m, 1H), 4.24 (m, 1H), 4.17 (m, 1H); MS (ESI) m/z 273 (M+H⁺).

AD-CB-024S-WZ02033

Compound AD-CB-024S-WZ02033 was prepared using the same procedure forthe preparation of AD-CB-010S-WZ01183. For the major rotomer: ¹H NMR(400 MHz, acetone-d6) δ 10.19 (s, 1H), 9.31 (s, 1H), 8.38 (d, J=1.6 Hz,1H), 8.11 (d, J=2.0 Hz, 1H), 7.88 (d, J=8.2 Hz, 2H), 7.19 (dd, J=8.4,2.0 Hz, 1H), 7.03 (d, J=2.0 Hz, 1H), 6.79 (dd, J=8.4, 2.0 Hz, 1H), 4.62(m, 1H), 4.50 (m, 1H), 4.20 (m, 2H), 3.88 (m, 2H), 3.83 (m, 1H), 3.75(m, 1H); MS (ESI) m/z 317 (M+H⁺).

AD-CB-013S-WZ-02001

A mixture of palladium acetate (37 mg, 0.165 mmol) and BINAP (154 mg,0.248 mmol) in 5 mL dioxane was stirred for 10 min under Ar atmosphere.To this mixture was added 1-bromo-4-nitrobenzene (1.11 g, 5.5 mmol),4-methoxyaniline (745 mg, 6.07 mmol), CsCO₃ (2.5 g, 7.73 mmol), and 10mL of dioxane. The mixture was heated at reflux for 15 h and cooled anddiluted with ether (80 mL). The solid was removed through filtration andthe filtrate was concentrated. The residue was chromatographed(hexane/EtOAc) to afford 4-methoxy-N-(4-nitrophenyl)aniline as a yellowsolid (786 mg, 58%). MS (ESI) m/z 245 (M+H⁺).

To 4-methoxy-N-(4-nitrophenyl)aniline (785 mg, 3.2 mmol) in 5 mL of AcOHwas added Pd(OAc)₂ (1.43 g, 6.4 mmol). The mixture was heated at 100° C.for 15 h under air atmosphere and cooled to rt and concentrated underreduced pressure. The residue was taken up in EtOAc (100 mL) and washedwith NaHCO₃ (2×100 mL) and water (100 mL). After solvent removal, thecrude was purified with chromatography (hexane/EtOAc) to afford3-methoxy-6-nitro-9H-carbazole as a orange solid (495 mg, 64%). ¹H NMR(400 MHz, acetone-d6) δ 10.90 (s, 1H), 9.09 (d, J=2.4 Hz, 1H), 8.27 (dd,J=9.2, 2.4 Hz, 1H), 7.96 (d, J=2.4 Hz, 1H), 7.62 (d, J=9.2 Hz, 1H), 7.53(d, J=8.8 Hz, 1H), 7.14 (dd, J=8.8, 2.8 Hz, 1H), 3.92 (s, 3H); MS (ESI)m/z 243 (M+H⁺).

To 3-methoxy-6-nitro-9H-carbazole (100 mg, 0.41 mmol) in 40 mL MeOH wasadded Palladium on activated carbon (50 mg). The mixture was stirred atrt under H2 atmosphere for 5 h. Solid was filtered off and the filtratewas concentrated to afford 6-methoxy-9H-carbazol-3-amine as a brownsolid (80 mg, 92%). This material was used directly for the nextreaction without purification. MS (ESI) m/z 213 (M+H⁺).

To 6-methoxy-9H-carbazol-3-amine (16 mg, 0.075 mmol) and1-bromo-2-fluoroethane (48 mg, 0.375 mmol) in 0.3 mL of NMP was addedCs₂CO₃ (30 mg, 0.09 mmol). The mixture was stirred at rt for 72 h underAr atmosphere and diluted with EtOAc (30 mL). It was washed with water(3×30 mL) and dried over MgSO₄. After solvent removal, the residue waspurified by reversed-phase HPLC (buffer A: 0.05% aqueous TFA; buffer B:0.05% TFA in MeCN) to afford a light-brown wax (5 mg, 26%). ¹H NMR (400MHz, acetone-d6) δ 7.75 (s, 1H), 7.67 (s, 1H), 7.52 (d, J=2.4 Hz, 1H),7.35 (t, J=9.6 Hz, 2H), 7.14 (d, J=8.0 Hz, 1H), 7.00 (dd, J=8.8, 2.4 Hz,1H), 4.81 (t, J=5.2 Hz, 1H), 4.69 (t, J=4.8 Hz, 1H), 3.89 (s, 3H); MS(ESI) m/z 259 (M+H⁺).

AD-C-004S-WZ01055

To 7,8-dihydroxy-4-phenyl-2H-chromen-2-one (500 mg, 2 mmol) and3,4-dihydro-2H-pyran in 4 mL THF and 4 mL DCM was added pyridiniumparatoluene sulfonate (PPTS, 8 mg). The mixture was stirred at rt for 15h under Ar atmosphere and diluted with EtOAc (50 mL). It was washed withNaHCO₃ (sat. 30 mL) and water (50 mL) and dried over MgSO₄ andconcentrated under reduced pressure. The residue was chromatographed(hexane/EtOAc) to afford8-hydroxy-4-phenyl-7-(tetrahydro-2H-pyran-2-yloxy)-2H-chromen-2-one as ayellow solid (180 mg, 26%). MS (ESI) m/z 339 (M+H⁺).

To 8-hydroxy-4-phenyl-7-(tetrahydro-2H-pyran-2-yloxy)-2H-chromen-2-one(40 mg, 0.12 mmol) and 1-bromo-2-fluoroethane (22 mg, 0.17 mmol) in 0.4mL NMP was added Cs₂CO₃ (46 mg, 0.14 mmol). The mixture was stirred atrt for 5 h under Ar atmosphere and diluted with ether (40 mL). It waswashed with water (3×30 mL) and dried over MgSO₄ and concentrated. Thecrude product was purified with chromatography (hexane/EtOAc) to afford8-(2-fluoroethoxy)-4-phenyl-7-(tetrahydro-2H-pyran-2-yloxy)-2H-chromen-2-oneas a white solid (34 mg, 73%). MS (ESI) m/z 385 (M+H⁺).

To8-(2-fluoroethoxy)-4-phenyl-7-(tetrahydro-2H-pyran-2-yloxy)-2H-chromen-2-onewas added 1.5 mL of a 4 M HCl dioxane solution. The mixture was stirredat rt for 30 min under Ar atmosphere and concentrated. The crude productwas purified with chromatography (hexane/EtOAc) to afford8-(2-fluoroethoxy)-7-hydroxy-4-phenyl-2H-chromen-2-one(AD-C-004S-WZ01055) as a white solid (24 mg, 90%). ¹H NMR (400 MHz,CDCl₃) δ 8.96 (s, 1H), 7.57-7.54 (m, 3H), 7.52-7.49 (m, 2H), 7.08 (dd,J=8.8, 1.2 Hz, 1H), 6.87 (dd, J=8.8, 1.2 Hz, 1 H), 6.11 (d, J=1.2 Hz,1H), 4.86 (m, 1H), 4.74 (m, 1H), 4.50 (m, 1H), 4.43 (m, 1H); MS (ESI)m/z 301 (M+H⁺), 323 (M+H⁺).

AD-C-004P-WZ01051

To 8-hydroxy-4-phenyl-7-(tetrahydro-2H-pyran-2-yloxy)-2H-chromen-2-one(115 mg, 0.34 mmol) and ethane-1,2-diylbis(4-methylbenzenesulfonate)(188 mg, 0.51 mmol) in 1 mL NMP was added Cs₂CO₃ (133 mg, 0.41 mmol).The mixture was stirred at rt for 15 h under Ar atmosphere and dilutedwith ether (50 mL). It was washed with water (3×50 mL) and dried overMgSO₄ and concentrated. The crude product was purified withchromatography (hexane/EtOAc) to2-(2-oxo-4-phenyl-7-(tetrahydro-2H-pyran-2-yloxy)-2H-chromen-8-yloxy)ethyl4-methylbenzenesulfonate as a white wax (97 mg, 53%). ¹H NMR (400 MHz,CDCl₃) δ 7.83 (d, J=8.4 Hz, 1H), 7.53-7.50 (m, 3H), 7.43-7.41 (m, 2 h),7.36 (d, J=8.0 Hz, 1H), 7.16 (d, J=8.8 Hz, 1H), 7.06 (d, J=9.2 Hz, 1H),6.22 (s, 1H), 5.56 (t, J=2.8 Hz, 1H), 4.41 (m, 4H), 3.86 (td, J=10.8,2.8 Hz, 1H), 3.61 (m, 1H), 2.08-1.86 (m, 3H), 1.76-1.63 (m, 3H); MS(ESI) m/z 537 (M+H⁺).

AD-F-001S-WZ01067

To 1-(2,4-dihydroxyphenyl)ethanone (1.52 g, 10 mmol) in 12 mL acetonewas added K2CO3 (1.38 g, 10 mmol) followed by slow addition ofchloro(methoxy)methane (885 mg, 11 mmol) with stirring under Aratmosphere at rt. The reaction mixture was stirred at rt for 4 h andfiltered. Solid was washed with EtOAc (80 mL) and the combined filtratewas washed with NaH₂PO₄ (sat. 50 mL) and water (80 mL) and dried overMgSO₄ and concentrated. The crude product was purified with silicachromatography (hexane/EtOAc) to afford1-(2-hydroxy-4-(methoxymethoxy)phenyl)ethanone as a off-white solid (1.2g, 61%). MS (ESI) m/z 197 (M+H⁺).

A mixture of 3,4-dihydroxybenzaldehyde (1.38 g, 10 mmol), benzyl bromide(1.71 g, 10 mmol), and K₂CO₃ (1.24 g, 9 mmol) in 20 mL acetone wasstirred at rt for 15 h under Ar atmosphere. Solid was filtered off andthe filtrated was diluted with EtOAc (100 mL) and washed with NaH₂PO₄(sat. 100 mL), and dried over MgSO₄ and concentrated. The residue waschromatographed (hexane/EtOAc) to afford4-(benzyloxy)-3-hydroxybenzaldehyde as a white solid (1.15 g, 50%). ¹HNMR (400 MHz, CDCl₃) δ 9.84 (s, 1H), 7.46 (d, J=2.0 Hz, 1H), 7.44-7.40(m, 6H), 7.04 (d, J=8.0 Hz, 1H), 5.80 (s, 1H), 5.21 (s, 2H); MS (ESI)m/z 229 (M+H⁺).

A mixture of 4-(benzyloxy)-3-hydroxybenzaldehyde (912 mg, 4 mmol),chloro(methoxy)methane (480 mg, 6 mmol), and DIPEA (1.03 g, 8 mmol) in20 mL DCM was stirred at rt under Ar atmosphere for 15 h. It was dilutedwith ether (100 mL) and washed with 0.5 M HCl(2×50 mL) and water (2×80mL), dried over MgSO₄ and concentrated. The crude product was purifiedwith silica chromatography (hexane/EtOAc) to afford4-(benzyloxy)-3-(methoxymethoxy)benzaldehyde as a clear oil (960 mg,88%). MS (ESI) m/z 273 (M+H⁺).

To 1-(2-hydroxy-4-(methoxymethoxy)phenyl)ethanone (618 mg, 3.15 mmol)and 4-(benzyloxy)-3-(methoxymethoxy)benzaldehyde (816 mg, 3 mmol) in a25-mL round-bottom flask under Ar atmosphere was added 2.5 mL of afreshly made 5% KOH in EtOH solution. The mixture was vigorously stirredat rt until it solidified and kept at rt for 6 days. It was taken up inether (100 mL) and added 0.5 M HCl to pH=5, and stirred for 3 min. Themixture was washed with water (2×100 mL) and dried over MgSO₄ andconcentrated. The residue was chromatographed (hexane/EtOAc) to afford(E)-3-(4-(benzyloxy)-3-(methoxymethoxy)phenyl)-1-(2-hydroxy-4-(methoxymethoxy)phenyl)prop-2-en-1-oneas a clear oil (780 mg, 58%). MS (ESI) m/z 451 (MAI).

To(E)-3-(4-(benzyloxy)-3-(methoxymethoxy)phenyl)-1-(2-hydroxy-4-(methoxymethoxy)phenyl)prop-2-en-1-one(450 mg, 1 mmol) in 1.5 mL MeOH was added 4 mL of a 15% NaOH solution,followed by hydrogen peroxide (113 mg, 30% solution). The mixture wasstirred at rt for 2 h and additional 226 mg of hydrogen peroxide wasadded. The reaction was stirred for 15 and quenched onto NaH₂PO₄ (sat.50 mL). It was extracted with EtOAc (3×50 mL) and the combined organicphase was dried over MgSO₄ and concentrated. The residue waschromatographed (hexane/EtOAc) to afford2-(4-(benzyloxy)-3-(methoxymethoxy)phenyl)-3-hydroxy-7-(methoxymethoxy)-4H-chromen-4-oneas a off-white solid (55 mg, 12%). MS (ESI) m/z 465 (M+H⁺).

To2-(4-(benzyloxy)-3-(methoxymethoxy)phenyl)-3-hydroxy-7-(methoxymethoxy)-4H-chromen-4-one(55 mg, 0.12 mmol) in 2 mL of DCM was added DIPEA (31 mg, 0.24 mmol),followed by slow addition of chloro(methoxy)methane (15 mg, 0.18 mmol).The reaction mixture was stirred at rt under Ar atmosphere for 3 h anddiluted with ether (30 mL). It was washed with water (3×30 mL) and driedover MgSO₄ and concentrated. The crude product was purified with silicachromatography (hexane/EtOAc) to afford2-(4-(benzyloxy)-3-(methoxymethoxy)phenyl)-3,7-bis(methoxymethoxy)-4H-chromen-4-oneas a white solid (55 mg, 90%). ¹H NMR (400 MHz, CDCl₃) δ 8.14 (d, J=8.8hz, 1H), 7.91 (d, J=2.0 Hz, 1H), 7.71 (dd, J=8.4 Hz, 2.0 Hz, 1H),7.46-7.44 (m, 2H), 7.39 (m, 2H), 7.34-7.31 (m, 1H), 7.12 (d, J=2.4 Hz,1H), 7.05 (dd, J=8.8, 2.4 Hz, 1H), 7.03 (d, J=8.4 Hz, 1H), 5.30 (s, 2H),5.28 (s, 2H), 5.24 (s, 2H), 5.21 (s, 2H), 3.55 (s, 3H), 3.51 (s, 3H),3.18 (s, 3H); MS (ESI) m/z 509 (M+H⁺).

To2-(4-(benzyloxy)-3-(methoxymethoxy)phenyl)-3,7-bis(methoxymethoxy)-4H-chromen-4-one(55 mg, 0.108 mmol) in 10 mL MeOH was added Palladium on activatedcarbon (20 mg). The mixture was stirred at rt under H₂ atmosphere for 2h. Solid was filtered off and the filtrate was concentrated to afford2-(4-hydroxy-3-(methoxymethoxy)phenyl)-3,7-bis(methoxymethoxy)-4H-chromen-4-oneas a yellow solid (45 mg, 99%). This material was used directly for thenext reaction without purification. MS (ESI) m/z 419 (M+H⁺).

To2-(4-hydroxy-3-(methoxymethoxy)phenyl)-3,7-bis(methoxymethoxy)-4H-chromen-4-one(20 mg, 0.048 mmol) and 1-bromo-2-fluoroethane (18 mg, 0.14 mmol) in 0.3mL NMP was added Cs₂CO₃ (39 mg, 0.12 mmol). The mixture was stirred atrt for 15 h under Ar atmosphere and diluted with ether (30 mL). It waswashed with NaH₂PO₄ (sat. 30 mL) and water (2×30 mL) and dried overMgSO₄ and concentrated. The crude product was purified withchromatography (hexane/EtOAc) to afford2-(4-(2-fluoroethoxy)-3-(methoxymethoxy)phenyl)-3,7-bis(methoxymethoxy)-4H-chromen-4-oneas a white solid (19 mg, 85%). ¹H NMR (400 MHz, CDCl₃) δ 8.15 (d, J=8.8Hz, 1H), 7.91 (d, J=2.0 Hz, 1H), 7.76 (dd, J=8.4 Hz, 2.0 Hz, 1H), 7.13(d, J=2.4 Hz, 1H), 7.05 (dd, J=8.8, 2.4 Hz, 1H), 7.03 (d, J=8.4 Hz, 1H),5.29 (s, 4H), 5.22 (s, 2H), 4.89 (m, 1H), 4.78 (m, 1H), 4.40 (m. 1H),4.32 (m, 1H), 3.56 (s, 3H), 3.51 (s, 3 H) 3.20 (s, 3H); MS (ESI) m/z 465(M+H⁺).

To2-(4-(2-fluoroethoxy)-3-(methoxymethoxy)phenyl)-3,7-bis(methoxymethoxy)-4H-chromen-4-one(19 mg, 0.041 mmol) was added 1 mL of 4 M HCl solution in dioxane. Themixture was stirred at rt for 3 h. Volatiles were removed under reducedpressure and the residue was washed with ether (2×1 mL) and dried underhigh vacuum to afford2-(4-(2-fluoroethoxy)-3-hydroxyphenyl)-3,7-dihydroxy-4H-chromen-4-one(AD-F-001S-WZ01067) as a yellow solid (11 mg, 81%). ¹H NMR (400 MHz,DMSO-d6) δ 10.73 (s, 1H), 9.39 (s, 1H), 9.17 (s, 1H), 7.89 (d, J=9.6 Hz,1H), 7.69 (d, J=2.0 Hz, 1H), 7.59 (dd, J=8.4 Hz, 2.0 Hz, 1H), 7.06 (d,J=8.8 Hz, 1H), 6.87 (m, 2H), 4.80 (m, 1H), 4.68 (m, 1H), 4.30 (m, 1H),4.23 (m, 1H); MS (ESI) m/z 333 (M+H⁺), 355 (M+Na⁺).

AD-C-001P-WZ01079

To2-(4-hydroxy-3-(methoxymethoxy)phenyl)-3,7-bis(methoxymethoxy)-4H-chromen-4-one(19 mg, 0.045 mmol) and 2-bromoethanol (44 mg, 0.36 mmol) in 0.2 mL NMPwas added Cs₂CO₃ (29 mg, 0.09 mmol). The mixture was stirred at rt for15 h under Ar atmosphere and diluted with ether (30 mL). It was washedwith NaH₂PO₄ (sat. 30 mL) and water (2×30 mL) and dried over MgSO₄ andconcentrated. The crude product was purified with chromatography(hexane/EtOAc) to2-(4-(2-hydroxyethoxy)-3-(methoxymethoxy)phenyl)-3,7-bis(methoxymethoxy)-4H-chromen-4-one(18 mg, 86%). MS (ESI) m/z 463 (M+H⁺).

To2-(4-(2-hydroxyethoxy)-3-(methoxymethoxy)phenyl)-3,7-bis(methoxymethoxy)-4H-chromen-4-one(18 mg, 0.039 mmol) and DIPEA (15 mg, 0.11 mmol) was added4-methylbenzene-1-sulfonyl chloride (11 mg, 0.058 mmol). The mixture wasstirred at rt for 15 h under Ar atmosphere and diluted with ether (30mL). It was washed with 0.5 M HCl(2×30 mL) and water (50 mL), and driedover MgSO₄ and concentrated. The crude product was chromatographed toafford2-(4-(3,7-bis(methoxymethoxy)-4-oxo-4H-chromen-2-yl)-2-(methoxymethoxy)phenoxy)ethyl4-methylbenzenesulfonate (AD-C-001P-WZ01079) as a yellow wax (20 mg,83%). ¹H NMR (400 MHz, CDCl₃) δ 8.15 (dd, J=8.8, 2.0 Hz, 1H), 7.89 (d,J=2.0 Hz, 1H), 7.76 (dd, J=8.4 Hz, 2.0 Hz, 2H), 7.73 (dd, J=8.4, 2.0 Hz,1H), 7.36 (d, J=6.8 Hz, 2H), 7.27 (d, J=2.0 Hz, 1H), 7.14 (d, J=2.4 Hz,1H), 7.05 (dd, J=8.8, 2.0 Hz, 1H), 6.94 (dd, J=8.8, 2.0 Hz, 1H), 5.29(d, J=1.6 Hz, 2H), 5.22 (d, J=2.0 Hz, 4H), 4.42 (t, J=3.0 Hz, 2H), 4.32(t, J=3.0 Hz, 2H), 3.53 (d, J=2.4 Hz, 3H), 3.52 (d, J=2.0 Hz, 3H), 3.20(d, J=2.4 Hz, 3H), 2.46 (s, 3H); MS (ESI) m/z 617 (M+H⁺).

Synthetic Scheme of CB 14-16, 19 and 20

7-((4-fluorobutyl)(methyl)amino)-9H-carbazol-2-ol (CB-14)

To a round bottom flask containing Compound 6 (21 mg, 0.073 mmol) in DMF(1 ml), were added cesium carbonate (28.5 mg, 0.087 mmol) and1-bromo-4-fluorobutane (56.4 mg, 0.364 mmol). The reaction was stirredat rt for 30 min. The reaction was work-up with EtOAc (15 mL×3) andwater (10 mL). The organic layers were washed with brine (10 mL), driedand concentrated in vacuo. The residue was dissolved in MeOH (10 ml). Tothe reaction mixture, was added Pd/C (22 mg). The mixture was stirred atrt overnight under hydrogen (1 atm). The reaction was filtered through acelite plug, concentrated in vacuo and purified on HPLC to afford CB-14(11 mg, 0.029 mmol, 40.3% yield). ¹H-NMR (400 MHz, CD₃OD) δ: 8.74 (d,J=8.4 Hz, 1H), 7.85 (d, J=8.4 Hz, 1H), 7.53 (s, 1H), 7.25 (d, J=8.0 Hz,1H), 6.85 (s, 1H), 6.73 (d, J=8.4 Hz, 1H), 4.44 (m, 1H), 4.32 (m, 1H),3.70 (m, 2H), 3.35 (s, 3H), 1.74-1.67 (m, 4H); LRMS for C₁₉H₁₉F₄N₂O₂+H⁺,calc'd: 384.1. found: 287.2 (M+H⁺-TFA).

7-((2-fluoroethyl)(methyl)amino)-9H-carbazol-2-ol (CB-15)

To a round bottom flask containing Compound 6 (37 mg, 0.122 mmol) in DMF(0.5 ml), were added cesium carbonate (47.8 mg, 0.147 mmol) and1-bromo-2-fluoroethane (78 mg, 0.612 mmol). The reaction was stirred atrt for 30 min. The reaction was work-up with EtOAc (15 mL×3) and water(10 mL). The organic layers were washed with brine (10 mL), dried andconcentrated in vacuo. The residue was dissolved in MeOH (10 ml). To thereaction mixture, was added Pd/C (22 mg). The mixture was stirred at rtovernight under hydrogen (1 atm). The reaction was filtered through acelite plug, concentrated in vacuo and purified on HPLC to afford CB-15(5 mg, 0.019 mmol, 7.3% yield). ¹H-NMR (400 MHz, CD₃CN) δ: 7.96 (d,J=8.0 Hz, 1H), 7.87 (d, J=8.4 Hz, 1H), 7.31 (d, J=2.0 Hz, 1H), 7.05 (dd,J=8.0 Hz, 2.0 Hz, 1H), 6.90 (d, J=2.0 Hz, 1H), 6.76 (dd, J=8.0 Hz, 2.0Hz, 1H), 4.86 (m, 1H), 4.74 (m, 1H), 4.60-4.52 (m, 2H), 3.28 (br, 1H),3.03 (s, 3H); LRMS for C₁₇H₁₅F₄N₂O₂+H⁺, calc'd: 356.1. found: 259.2(M+H⁺-TFA).

7-(2-fluoroethylamino)-9H-carbazol-2-ol (CB-16)

To a round bottom flask containing Compound 5 (21 mg, 0.073 mmol) in DMF(1 ml), were added cesium carbonate (28.5 mg, 0.087 mmol) and1-bromo-2-fluoroethane (46 mg, 0.36 mmol). The reaction was stirred atrt for 72 hours. The reaction was work-up with EtOAc (15 mL×3) and water(10 mL). The organic layers were washed with brine (10 mL), dried andconcentrated in vacuo. The residue was dissolved in MeOH (10 ml). To thereaction mixture, was added Pd/C (20 mg). The mixture was stirred at rtovernight under hydrogen (1 atm). The reaction was filtered through acelite plug, concentrated in vacuo and purified on HPLC to afford CB-16(5 mg, 0.015 mmol, 20% yield). ¹H-NMR (400 MHz, CD₃CN) δ: 9.00 (br, 1H),7.77-7.73 (m, 2H), 6.82 (s, 1H), 6.81 (s, 1H), 6.72-6.65 (m, 2H), 4.71(m, 1H), 4.60 (m, 1H), 3.60-3.50 (m, 2H); LRMS for C₁₆H₁₃F₄N₂O₂+H⁺,calc'd: 342.3. found: 245.1 (M+H⁺-TFA).7((2-(2-(2-fluoroethoxy)ethoxy)ethyl)(methyl)amino)-9H-carbazol-2-ol(CB-19)

To a round bottom flask containing Compound 6 (41 mg, 0.14 mmol) in DMF(0.5 ml), were added cesium carbonate (53 mg, 0.16 mmol) and2-(2-(2-fluoroethoxy)ethoxy)ethyl 4-methylbenzenesulfonate (125 mg,0.407 mmol). The reaction was stirred at rt for 4 weeks. The reactionwas work-up with EtOAc (15 mL×3) and water (10 mL). The organic layerswere washed with brine (10 mL), dried and concentrated in vacuo. Theresidue was dissolved in MeOH (10 ml). To the reaction mixture, wasadded Pd/C (20 mg). The mixture was stirred at rt overnight underhydrogen atmosphere (1 atm). The reaction was filtered through a celiteplug, concentrated in vacuo and purified on HPLC to afford CB-19 (7 mg,0.020 mmol, 14% yield. ¹H-NMR (400 MHz, CD₃CN) δ: 9.43 (br, 1H), 8.07((d, J=8.4 Hz, 1H), 7.91 (d, J=8.4 Hz, 1H), 7.58 (d, J=2.4 Hz, 1H), 7.24(dd, J=8.0 Hz, 2.0 Hz, 1H), 6.93 (d, J=2.0 Hz, 1H), 6.77 (dd, J=8.0 Hz,2.0 Hz, 1H), 4.59 (m, 1H), 4.52 (m, 1H), 3.74-3.50 (m, 10H), 3.28 (s,3H); LRMS for C₂₁H₂₃F₄N₂O₄+Na⁺, calc'd: 444.2. found: 347.2 (M+H⁺-TFA).

7-(2-fluoroethoxy)-N-methyl-9H-carbazol-2-amine (CB-20)

To a round bottom flask containing Compound 6 (90 mg, 0.29 mmol) in MeOH(10 ml), were added Pd/C (20 mg). The reaction was purged with hydrogenand stirred at rt for 2 h under hydrogen atmosphere (1 atm). Thereaction was filtered through a celite plug concentrated in vacuo toafford a dark solid (60 mg, 0.28 mmol, 95% yield). To a round bottomflask containing the above dark solid (15 mg, 0.071 mmol) in DMF (0.5mL), was added cesium carbonate (21 mg, 0.65 mmol) and2-bromo-1-fluoroethane (8.1 mg, 0.065 mmol). The reaction was stirred atrt overnight. The reaction was concentrated in vacuo via MeCNco-evaporation. The residue was purified on HPLC to afford CB-20 (7.0mg, 0.027 mmol, 38% yield). ¹H NMR (400 MHz, CD₃CN) δ: 9.52 (br, 1H),7.91-7.86 (m, 2H), 7.13 (s, 1H), 7.02 (s, 1H), 6.88 (d, J=7.6 Hz, 1H),6.82 (dd, J=7.6 Hz, J=2.4 Hz 1H), 4.85 (m, 1H), 4.72 (m, 1H), 4.34-4.25(m, 2H), 2.96 (s, 3H); LRMS for C₁₇H₁₅N₂O₂+H⁺, calc'd: 356.1. found:259.1 (M+H⁺-TFA).

Synthetic Scheme of CB 25, 26:

4′-(benzyloxy)-2′-nitrobiphenyl-4-ol (Compound 7)

A round bottom flask charged with Compound 2 (1.96 g, 7.44 mmol),4-Hydroxyphenylboronic acid pinacol ester (1.56 g, 7.09 mmol),terakis(triphenylphosphine) palladium (0.410 g, 0.354 mmol), were purgedwith Argon. To the mixture, was added DME (10 ml) and potassiumcarbonate (1.96 g, 14.2 mmol) in Water (2 ml). The mixture was heatedfor 60 hours. The reaction was diluted with HCl (1N, 10 mL) and brine(40 mL), then extracted with EtOAc (50 mL×3). The combined organic layerwere washed with Brine (50 mL), dried (MgSO₄) and concentrated in vacuo.The residue was purified on a silica gel column (EtOAc: Hexanes=1:4) toafford Compound 7 as a yellow solid (2 g, 6.22 mmol, 88% yield). ¹H-NMR(400 MHz, CDCl₃) δ: 7.45-7.33 (m, 7H), 7.37-7.15 (m, 3H), 6.88-6.85 (m,2H), 5.14 (s, 2H), 5.03 (s, 1H); LRMS for C₁₉H₁₅NO₄+H⁺, calc'd: 322.1.found: 322.1 (M+H⁺).

7-(benzyloxy)-9H-carbazol-2-ol (Compound 8)

To a pressure resistant vial, was added Compound 7 (2.00 g, 6.22 mmoland Triethyl phosphite (6.53 ml, 37.3 mmol. The mixture was heated to160° C. overnight. The reaction mixture was concentrated in vacuo. Theresidue was suspended in chloroform (20 mL), solid precipitate formedand was filtered and washed with ether (10 mL×2) to afford Compound 8(900 mg, 3.11 mmol, 50.0% yield). ¹H-NMR (400 MHz, DMSO) δ: 10.81 (br,1H), 9.25 (br, 1H), 7.80 (d, J=8.4 Hz, 1H), 7.72 (d, J=8.4 Hz, 1H),7.50-7.33 (m, 5H), 6.95 (s, 1H), 6-78-6.76 (m, 2H), 6.56 (dd, J=8.4, 2.0Hz 1H), 5.16 (s, 2H); LRMS for C₁₉H₁₅NO₂+H⁺, calc'd: 290.1. found: 290.1(M+H⁺).

7-(2-fluoroethoxy)-9H-carbazol-2-ol (CB-25)

To a round bottom flask containing Compound 8 (50 mg, 0.17 mmol) in DMF(1 ml), was added cesium carbonate (62 mg, 0.19 mmol) and1-bromo-2-fluoroethane (33 mg, 0.26 mmol). The reaction was stirred atrt for 15 h and then diluted with water (15 mL). White precipitate (50mg) was collected via filtration and dried in vacu. The solid wasdissolved in MeOH (10 mL). To the reaction, was added Pd/C (30 mg) andacetic acid (5 drops). The mixture was stirred under hydrogen (1 atm)atmosphere for 20 h and then filtered through a celite plug,concentrated in vacuo. The residue was purified on HPLC to afford CB-25(18 mg, 0.053 mmol, 31% yield). ¹H NMR (400 MHz, CD₃CN) δ: 8.99 (br,1H), 7.72 (d, J=8.4 Hz, 1H), 7.67 (d, J=8.4 Hz, 1H), 6.88 (d, J=2.0 Hz,1H), 6.76 (d, J=2.0 Hz, 1H), 6.67 (dd, J=8.0 Hz, 2.0 Hz, 1H), 6.58 (dd,J=8.0 Hz, 2.0 Hz, 1H), 4.75-4.74 (m, 1H), 4.63-4.61 (m, 1H), 4.23-4.13(m, 2H); LRMS for C₁₆H₁₂F₄NO₃+H⁺, calc'd: 343.1. found: 246.0(M+H⁺-TFA).

7-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-9H-carbazol-2-ol (CB-26)

To a round bottom flask containing Compound 8 (50 mg, 0.17 mmol) in DMF(1 ml), was added cesium carbonate (56 mg, 0.17 mmol) and2-(2-(2-fluoroethoxy)ethoxy)ethyl 4-methylbenzenesulfonate (53 mg, 0.17mmol). The reaction was stirred at rt for 15 h and then diluted withwater (15 mL). White precipitate (72 mg) was collected via filtrationand dried in vacou. The solid was dissolved in MeOH (10 mL). To thereaction, was added Pd/C (20 mg) and acetic acid (5 drops). The mixturewas stirred under hydrogen (1 atm) atmosphere for 20 h and then filteredthrough a celite plug and concentrated in vacuo. The residue waspurified on HPLC to afford CB-26 (20 mg, 0.046 mmol, 27% yield). ¹H NMR(400 MHz, CD₃CN) δ: 9.03 (br, 1H), 7.81-7.75 (m, 2H), 6.96 (d, J=2.4 Hz,1H), 6.84 (d, J=2.4 Hz, 1H), 6.76 (dd, J=7.6 Hz, 2.0 Hz, 1H), 6.67 (dd,J=7.6 Hz, 2.0 Hz, 1H), 4.59-4.57 (m, 1H), 4.47-4.45 (m, 1H), 4.17-4.15(m, 2H), 3.83-3.63 (m, 8H); LRMS for C₂₀H₂₀NO₅+H⁺, calc'd: 431.1. found:334.1 (M+H⁺-TFA).

Synthetic Scheme of CB 27:

tert-butyl 7-hydroxy-9H-carbazol-2-ylcarbamate (Compound 9)

To a round bottom flask containing Compound 4 (1.0 g, 2.6 mmol) in MeOH(150 mL), was added palladium on charcoal (400 mg). The flask was purgedwith hydrogen gas and stirred under hydrogen atmosphere overnight. Thereaction mixture was filtered through a celite plug and concentrated toafford Compound 9 as a grey solid (700 mg, 2.34 mmol, 90% yield). ¹H NMR(400 MHz, (CD₃)₂CO) δ: 9.99 (br, 1H), 8.41 (br, 1H), 8.24 (s, 1H), 7.86(s, 1H), 7.81-7.78 (m, 2H), 7.18 (dd, J=8.4 Hz, 2.0 Hz, 1H), 6.90 (d,J=2.0 Hz, 1H), 6.70 (dd, J=8.4 Hz, 2.0 Hz, 1H), 1.51 (s, 9H).

tert-butyl 7-(4-nitrophenoxy)-9H-carbazol-2-ylcarbamate (Compound 10)

To a round bottom flask containing Compound 9 (80 mg, 0.268 mmol) in DMF(2 mL) was added potassium carbonate (74.1 mg, 0.536 mmol) and4-fluoro-nitrobenzene (41.6 mg, 0.295 mmol). The reaction mixture washeated for 20 min at 140° C. After cooling down to rt, the mixture wasdiluted with water (20 mL) and extracted with EtOAc (20 mL×3). Theorganic layers were dried, concentrated. The residue was purified on asilica gel column (EtOAc: Hexanes=3:7) to afford Compound 10 as a yellowsolid (50 mg, 0.12 mmol, 44% yield). ¹H NMR (400 MHz, CDCl₃) δ: 8.22 (d,J=9.2 Hz, 2H), 8.10 (br, 1H), 8.00-7.90 (m, 3H), 7.12 (s, 1H), 7.06-6.90(m, 4H), 6.70 (br, 1H), 1.56 (s, 9H); LRMS for C₂₃H₂₁N₃O₅+H⁺, calc'd:420.2. found: 420.2 (M+H⁺).

tert-butyl 7-(4-nitrophenoxy)-9H-carbazol-2-ylcarbamate (CB-27)

To a round bottom flask containing Compound 10 (35 mg, 0.083 mmol) inMeOH (5 mL), was added palladium on charcoal (10 mg). The flask waspurged with hydrogen gas and stirred under hydrogen atmosphereovernight. The reaction mixture was filtered through a silica gel plugand concentrated to afford the amine intermediate (23 mg). To a vialcontaining 2-fluoropropanoic acid (10.87 mg, 0.118 mmol) in DCM (1 mL),was added EDC (22.64 mg, 0.118 mmol) and DMAP (1 mg). The mixture wasstirred at rt for 5 min. The above amine intermediate was dissolved inDCM (1 ml) and added into the reaction vial dropwise. The reactionmixture was stirred at rt from 3 hour. The reaction mixture was thenwashed with water (3 mL) and concentrated. The residue was redissolvedin HCl (4.0 M in dioxane, 5 mL) and stirred overnight. The mixture wasconcentrated and purified on HPLC to afford CB-27 (12 mg, 0.026 mmol,31% yield). ¹H NMR (400 MHz, CD₃CN) δ: 9.42 (br, 1H), 8.69 (br, 1H),7.92 (d, J=8.4 Hz, 1H), 7.87 (d, J=8.4 Hz, 1H), 7.60 (m, 2H), 7.04-7.01(m, 4H), 6.86 (d, J=8.0 Hz, 1H), 6.84 (d, J=8.0 Hz, 1H), 5.11 (dt,J=49.2, 6.8 Hz, 1H), 1.58 (dd, J=24.8, 6.8 Hz, 3H); LRMS forC₂₃H₁₈F₄N₃O₃+H⁺, calc'd: 460.1. found: 364.1 (M+H⁺-TFA).

Experimental Section for the Preparation of Carbazole Derivatives

4-(Benzyloxy)-N-(4-nitrophenyl)aniline 1: To a oven dried flask wascharged with Pd(OAc)₂ (81 mg, 0.36 mmol) and (S)-(−)-BINAP (336 mg, 0.54mmol), followed by toluene (10 mL). The mixture was stirred under Ar atroom temperature for 5 min. To this mixture was added 4-nitroiodobenzene(3.0 g, 12 mmol), 4-benzyloxyaniline hydrochloride (3.39 g, 14.4 mmol),Cs₂CO₃ (9.8 g, 30 mmol) and toluene (40 mL). The resulting mixture washeated under Ar at 100° C. for 16 hrs, and then cooled to roomtemperature and poured into H₂O (100 mL). The layers were separated. Theaqueous layer was extracted with EtOAc (3×20 mL). The combined organiclayers were washed with brine (2×20 mL), dried (MgSO₄) and filtered. Thefiltrate was concentrated. The residue was purified via columnchromatography (silica gel, 5-40% EtOAc/hexane) to give the desiredproduct as an orange solid (1.2 g, 31%). ¹H NMR (CDCl₃, 400 MHz) δ: 8.09(d, J=9.2 Hz, 2H), 7.30-7.49 (m, 5H), 7.15 (d, J=9.2 Hz, 2H), 7.01 (d,J=9.2 Hz, 2H), 6.77 (d, J=8.8 Hz, 2H), 6.10 (br s, 1H), 5.09 (s, 2H).MS: m/z=321 (M+H⁺)⁺.

3-(Benzyloxy)-9-nitro-9H-carbazole 2: A mixture of4-(benzyloxy)-N-(4-nitrophenyl)aniline 1 (0.5 g, 1.56 mmol) and Pd(OAc)₂(0.8 g, 3.56 mmol) in acetic acid (20 mL) was refluxed and monitored byTLC. After refluxing for 2 hrs, TLC showed that no starting material waspresent. It was concentrated in vacuo to remove acetic acid. The residuewas diluted with EtOAc (30 mL), washed with H₂O (20 mL), sat. NaHCO₃solution (2×20 mL), brine (20 mL), and then dried (MgSO₄) and filtered.The filtrate was concentrated in vacuo. The residue was purified viacolumn chromatography (silica gel, 5-40% EtOAc/hexane) to give thedesired product 2 as a dark yellow solid (100 mg, 20%). ¹H NMR(acetone-d₆, 400 MHz) δ: 10.92 (br s, 1H), 9.08 (d, J=2.0 Hz, 1H), 8.28(dd, J=8.8, 2.4 Hz, 1H), 8.07 (d, J=2.4 Hz, 1H), 7.63 (d, J=9.2 Hz, 1H),7.55 (d, J=8.8 Hz, 3H), 7.40 (t, J=7.2 Hz, 2H), 7.33 (t, J=7.2 Hz, 1H),7.24 (dd, J=8.8, 2.4 Hz, 1H), 5.26 (s, 2H). MS: m/z=319 (M+H⁺)⁺.

3-Amino-6-(benzyloxy)-9H-carbazole 3: To a suspension of3-(benzyloxy)-9-nitro-9H-carbazole 2 (100 mg, 0.31 mmol) and Cu(OAc)₂(57 mg, 0.31 mmol) in EtOH (20 mL) was added NaBH₄ (240 mg, 6.3 mmol).The resulting mixture was stirred at room temperature for 3 hrs, andthen concentrated in vacuo. The residue was dissolved in H₂O (30 mL),extracted with EtOAc (2×30 mL). The combined organic layers were dried(MgSO₄), filtered and concentrated in vacuo to give a solid (90 mg). Itwas used directly in the next step without any further purification. ¹HNMR (acetone-d₆, 400 MHz) δ: 9.67 (br s, 1H), 7.57 (d, J=2.4 Hz, 1H),7.52 (d, J=6.8 Hz, 2H), 7.39 (t, J=6.8 Hz, 2H), 7.26-7.33 (m, 3H), 7.19(d, J=8.8 Hz, 1H), 7.03 (dd, J=8.8, 2.4 Hz, 1H), 6.81 (dd, J=8.8, 2.4Hz, 1H), 5.17 (s, 2H), 4.24 (br s, 2H). MS: m/z=289 (M+HT.

6-(Benzyloxy)-N-methyl-9H-carbazol-3-amine 4: To a suspension of3-amino-6-(benzyloxy)-9H-carbazole 3 (90 mg, 0.31 mmol) andparaformaldehyde (47 mg, 1.57 mmol) in MeOH (20 mL) was added a solutionof NaOMe in MeOH (0.32 mL, 1.56 mmol). The resulting mixture was heatedat 80° C. for 1 h, then NaBH₄ (59 mg, 1.55 mmol) was added. Theresulting mixture was heated at 80° C. for 2 hrs, and then cooled toroom temperature. To this solution was added NaOH (1 N, 30 mL). Themixture was then extracted with CH₂Cl₂ (3×20 mL). The combined organiclayers were dried (MgSO₄), filtered. The filtrate was concentrated invacuo to give a brown solid (93 mg, 100%). It was used directly in thenext step without any further purification. ¹H NMR (acetone-d₆, 400 MHz)δ: 9.68 (br s, 1H), 7.67 (d, J=2.4 Hz, 1H), 7.53 (d, J=7.6 Hz, 2H),7.20-7.42 (m, 6H), 7.03 (dd, J=8.8, 2.4 Hz, 1H), 6.79 (dd, J=8.4, 2.4Hz, 1H), 5.17 (s, 2H), 2.85 (s, 3H). MS: m/z=303 (M+H⁺)⁺.

6-(Methylamino)-9H-carbazol-3-ol 5: A mixture of6-(benzyloxy)-N-methyl-9H-carbazol-3-amine 4 (93 mg, 0.31 mmol), Pd/C(10 mg) and acetic acid (10 drops) in MeOH (10 mL) was hydrogenated atroom temperature for 1.5 hrs. It was passed through a short Celite pad.The filtrate was concentrated in vacuo to give the desired product 5 (66mg). It was used directly in the next step without any furtherpurification. MS: m/z=213 (M+H⁺)⁺.

[3-(Benzyloxy)-6-(dimethylamino)-9H-carbazol-9-yl]methanol 7: To asolution of 6-(benzyloxy)-N-methyl-9H-carbazol-3-amine 4 (110 mg, 0.38mmol) and aqueous formaldehyde solution (37%, 1.0 mL) in acetonitrile(30 mL) was added NaB(OAc)₃ (323 mg, 1.52 mmol). The resulting mixturewas stirred at room temperature for 6 hrs, and then concentrated. Theresidue was dissolved in H₂O (30 mL), extracted with CH₂Cl₂ (2×30 mL).The combined organic layers were dried (MgSO₄), filtered. The filtratewas concentrated in vacuo to give the desired product (0.12 g). It wasused directly in the next step without any further purification. MS:m/z=347 (M+H⁺)⁺.

6-(Dimethylamino)-9-(methoxymethyl)-9H-carbazol-3-ol 8: A mixture of[3-(benzyloxy)-6-(dimethylamino)-9H-carbazol-9-yl]methanol 7 (120 mg,),Pd/C (100 mg) and acetic acid (cat. amount) in MeOH (15 mL) washydrogenated at room temperature for 4 hrs. It was filtered through ashort Celite pad. The filtrate was concentrated in vacuo to give thedesired product (94 mg, 100%). NMR (acetone-d₆, 400 MHz) δ: 7.38-7.50(m, 4H), 7.05 (dd, J=8.8, 2.4 Hz, 1H), 6.97 (dd, J=8.4, 2.4 Hz, 1H),5.62 (s, 2H), 3.20 (s, 3H), 2.94 (s, 6H). MS: m/z=271 (M+H⁺)⁺.

General procedures for the preparation of O-alkylated carbazolederivatives: To a solution of carbazol-3-ol derivatives (1 eq.) andCs₂CO₃ (1.5 eq.) in DMF (10 mL) was added a solution of2-(2-(2-fluoroethoxy)ethoxy)ethyl-4-methylbenzenesulfonate (1.2 eq.) inDMF (1.0 mL). The resulting mixture was stirred at room temperatureovernight, and then concentrated in vacuo. The residue was purified viacolumn chromatography (silica gel, 5-50% EtOAc/hexane) to provide thedesired products.

6-(2-(2-(2-Fluoroethoxy)ethoxy)ethoxy)-N-methyl-9H-carbazol-3-amine 6:(3 mg, 5%). ¹H NMR (acetone-d₆, 400 MHz) δ: 7.59 (d, J=2.4 Hz, 1H),7.28-7.33 (m, 2H), 7.26 (d, J=8.4 Hz, 1H), 6.97 (dd, J=8.8, 2.4 Hz, 1H),6.85 (dd, J=8.8, 2.0 Hz, 1H), 4.51 (dt, J=48, 4.0 Hz, 2H), 4.19 (t,J=4.4 Hz, 2H), 3.61-3.88 (m, 8H), 3.87 (s, 3H). MS: m/z=347 (M+H⁺)⁺.

6-(2-(2-(2-Fluoroethoxy)ethoxy)ethoxy)-9-(methoxymethyl)-N,N-dimethyl-9H-carbazol-3-amine9: (50 mg, 36%). NMR (acetone-d₆, 400 MHz) δ: 7.68 (d, J=2.4 Hz, 1H),7.46-7.52 (m, 3H), 7.04-7.08 (m, 2H), 5.66 (s, 2H), 4.52 (dt, J=48.4,4.4 Hz, 2H), 4.21 (t, J=4.8 Hz, 2H), 3.63-3.87 (m, 8H). MS: m/z=405(M+H⁺)⁺.

General procedures for the preparation of acylated carbazolederivatives: To a solution of2-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-9H-carbazole (1.0 eq.) in DMF(3.0 mL) was added NaH (excess). After stirring at room temperature for5 min, an acyl halide (excess) was added. The resulting mixture wasstirred at room temperature overnight, and then concentrated in vacuo.The residue was purified via column chromatography (silica gel, 0-40%EtOAc/hexane) to give the desired product.

1-(2-(2-(2-(2-Fluoroethoxy)ethoxy)ethoxy)-9H-carbazol-9-yl)ethanone: (4mg, 36%). ¹H NMR (CDCl₃, 400 MHz) δ: 8.21 (d, J=8.0 Hz, 1H), 7.99-8.25(m, 2H), 7.94 (d, J=2.4 Hz, 1H), 7.36-7.46 (m, 2H), 7.06 (dd, J=8.4, 2.4Hz, 1H), 4.52 (dt, J=48, 4.4 Hz, 2H), 4.27 (t, J=4.4 Hz, 2H), 3.89 (t,J=8.8 Hz, 2H), 3.64-3.78 (m, 6H), 2.91 (s, 3H). MS: m/z=360 (M+H⁺)⁺.

1-(2-(2-(2-(2-Fluoroethoxy)ethoxy)ethoxy)-9H-carbazol-9-yl)phenylmethanone:(51 mg, 78%). ¹H NMR (CDCl₃, 400 MHz) δ: 7.84-7.92 (m, 2H), 7.62-7.74(m, 3H), 7.53 (t, J=8.0 Hz, 2H), 7.27-7.33 (m, 2H), 7.17-7.23 (m, 1H),6.99 (dd, J=8.4, 2.4 Hz, 1H), 4.57 (dt, J=47.6, 4.4 Hz, 2H), 4.06 (t,J=4.8 Hz, 2H), 3.70-3.87 (m, 8H). MS: m/z=422 (M+H⁺)⁺.

Preparation of 2-(7-formamido-9H-carbazol-2-yloxy)ethyl4-methylbenzenesulfonate: AD-CB-012P-WZ02039

Compound 2-(7-formamido-9H-carbazol-2-yloxy)ethyl4-methylbenzenesulfonate (AD-CB-012P-WZ02039) was prepared using thesame procedure for the preparation of AD-CB-012S-WZ01185) fromN-(7-hydroxy-9H-carbazol-2-yl)formamide (100 mg) and ethane-1,2-diylbis(4-methylbenzenesulfonate) (325 mg). (white solid, 22 mg, 12%). Forthe major rotomer: ¹H NMR (400 MHz, acetone-d6) δ 10.19 (s, 1H), 9.31(s, 1H), 8.38 (d, J=1.6 Hz, 1H), 8.11 (d, J=2.0 Hz, 1H), 7.90-7.81 (m,4H), 7.45 (d, J=8.4 Hz, 2H), 7.19 (dd, J=8.4, 2.0 Hz, 1H), 6.95 (d,J=2.0 Hz, 1H), 6.69 (dd, J=8.4, 2.0 Hz, 1H), 4.43-4.41 (m, 2H),4.29-4.27 (m, 2H); MS (ESI) m/z 425 (M+H⁺).

Preparation of N-(7-(4-fluorobutoxy)-9H-carbazol-2-yl)formamide:AD-CB-30S-WZ02055

Compound N-(7-(4-fluorobutoxy)-9H-carbazol-2-yl)formamide(AD-CB-30S-WZ02055) was prepared using the same procedure for thepreparation of AD-CB-012S-WZ01185) fromN-(7-hydroxy-9H-carbazol-2-yl)formamide (20 mg) and1-bromo-4-fluorobutane (27 mg). (white solid, 11 mg, 42%). ¹H NMR (400MHz, acetone-d6) δ 10.18 (s, 1H), 9.31 (s, 1 H), 8.39 (d, J=2.0 Hz, 1H),8.11 (d, J=2.0 Hz, 1H), 7.95 (d, J=1.6 Hz, 2H), 7.88 (d, J=2.0 Hz, 1H),7.20 (dd, J=8.4, 2.0 Hz, 1H), 7.03 (d, J=2.4 Hz, 1H), 6.79 (dd, J=8.4,2.4 Hz, 1H), 4.61 (m, 1H), 4.49 (m, 1H), 4.11 (m, 2H), 1.97-1.88 (m,4H); MS (ESI) m/z 301 (M+H⁺).

Preparation of2-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-9H-pyrido[2,3-b]indol-7-aminehydrochloride

Preparation of WZ02045:

To 4-chloro-3-nitroaniline (2.5 g, 14.5 mmol) in 40 mL DCM was added TEA(2.9 g, 29 mmol), DMAP (177 mg, 1.45 mmol), and di-tert-butyldicarbonate (4.7 g, 21.7 mmol). The mixture was stirred at rt for 24 hand concentrated. The residue was diluted with Et2O (100 mL), washedwith brine (100 mL), water (100 mL), 0.5 M HCl (2×100 mL), and brine(100 mL), dried over MgSO₄ and concentrated. The crude product waspurified by silica chromatography (EtOAc/hexane) to afford tert-butyl4-chloro-3-nitrophenylcarbamate (WZ02045) as a yellow solid (1.5 g,38%). MS (ESI) m/z 295 (M+Na⁺).

Preparation of WZ02049:

A mixture of tert-butyl 4-chloro-3-nitrophenylcarbamate (818 mg, 3mmol),2-(benzyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine(933 mg, 3 mmol), tetrakis(triphenylphosphine)palladium (104 mg, 0.09mmol), 10 mL of dioxane, and 6 mL of 1 M Na₂CO₃ was heated at reflux for15 h. It was diluted with 50 mL Et₂O and washed with brine (2×50 mL) anddried over MgSO₄ and concentrated. The crude product was purified bysilica chromatography (EtOAc/hexane) to afford tert-butyl4-(6-(benzyloxy)pyridin-3-yl)-3-nitrophenylcarbamate (WZ02049) as ayellow wax (1.2 g, 95%). MS (ESI) m/z 444 (M+Na⁺).

Preparation of WZ02057:

A suspension of above compound (800 mg, 1.9 mmol) in 2 mL of triethylphosphite was heated at 148° C. for 15 h. After cooling, it wasconcentrated under reduced pressure to remove volatiles. The crudeproduct was purified by silica chromatography (EtOAc/hexane) to affordtert-butyl 2-(benzyloxy)-9H-pyrido[2,3-b]indol-7-ylcarbamate (WZ02057)as a off-white solid (400 mg, 54%). MS (ESI) m/z 390 (M+H⁺).

Preparation of WZ02061:

To above compound (220 mg, 0.56 mmol) dissolved in 80 mL MeOH was addedPalladium on activated carbon (80 mg). The mixture was stirred at rtunder H₂ atmosphere for 15 h. Solid was filtered off and the filtratewas concentrated to afford tert-butyl2-hydroxy-9H-pyrido[2,3-b]indol-7-ylcarbamate (WZ02061) as a white solid(105 mg, 100%). This material was used directly for the next reactionwithout purification. MS (ESI) m/z 300 (M+H⁺).

Preparation of WZ02063:

To above compound (50 mg, 0.167 mmol) in 1 mL of NMP was added2-(2-(2-fluoroethoxy)ethoxy)ethyl 4-methylbenzenesulfonate (76 mg, 0.25mmol), and Cs₂CO₃ (65 mg, 0.2 mmol). The mixture was stirred at rt for15 h and diluted with Et2O (40 mL), washed with water (3×30 mL), anddried over MgSO₄ and concentrated. The crude product was purified bysilica chromatography (EtOAc/hexane) to afford tert-butyl 2-(2-(2-(2fluoroethoxy)ethoxy)ethoxy)-9H-pyrido[2,3-b]indol-7-ylcarbamate(WZ02063) as a clear wax (45 mg, 62%). MS (ESI) m/z 434 (M+H⁺).

Preparation of AD-CB-032S-WZ02067:

The above compound (45 mg, 0.1 mmol) was treated with 2 mL of a 4 M HClin dioxane solution at rt for 5 h and concentrated under reducedpressure. The residue was washed with ether (5 mL) and dried under highvacuum to afford2-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-9H-pyrido[2,3-b]indol-7-aminehydrochloride (AD-CB-032S-WZ02067) as a light-yellow solid (23 mg, 62%).¹H NMR (400 MHz, methanol-d₄) δ 8.42 (d, J=8.4 Hz, 1H), 8.12 (d, J=8.4Hz, 1 H), 7.53 (d, J=2.0 Hz, 1H), 7.21 (dd, J=8.4, 2.0 Hz, 1H), 6.77 (d,J=8.4 Hz, 1H), 4.58-4.54 (m 3H), 4.43 (m, 1H), 3.91 (m, 2H), 3.76-3.72(m, 3H), 3.70-3.66 (m, 3H); MS (ESI) m/z 334 (M+H⁺).

Preparation of2-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-N-methyl-9H-pyrido[2,3-b]indol-7-amine:AD-CB-034S-WZ02069

Compound AD-CB-034S-WZ02069 was prepared using the same procedure forthe preparation of AD-CB-004S from2-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-9H-pyrido[2,3-b]indol-7-aminehydrochloride (AD-CB-032S-WZ02067, 20 mg) (10 mg, 53%). ¹H NMR (400 MHz,methanol-d4) δ 8.06 (d, J=8.0 Hz, 1H), 7.66 (d, J=8.4 Hz, 1H), 6.65 (d,J=2.0 Hz, 1H), 6.58 (dd, J=8.4, 2.0 Hz, 1H), 6.53 (d, J=8.0 Hz, 1H),4.58 (m 1H), 4.53-4.45 (m, 3H), 3.88 (m, 2 H), 3.76 (m, 1H), 3.73-3.67(m, 5H), 3.03 (s, 3H); MS (ESI) m/z 348 (M+H⁺).

Preparation of 6-bromo-9H-carbazol-2-ol: W138

Preparation of WZ02013:

To 9H-carbazol-2-ol (915 mg, 5 mmol) in 10 mL DMF and 20 mL DCM wasadded TEA (1.0 g, 10 mmol), followed by acetyl chloride (589 mg, 7.5mmol) at 0° C. The reaction mixture was then stirred at rt for 1 h andpoured onto ice (50 g). The mixture was extracted with EtOAc (2×60 mL)and combined organic phase was dried over MgSO₄ and concentrated. Thecrude product was purified by silica chromatography to afford9H-carbazol-2-yl acetate (WZ02013) as an off-white solid (800 mg, 71%).MS (ESI) m/z 348 (M+H⁺).

Preparation of WZ02025:

To a solution of 9H-carbazol-2-yl acetate (500 mg, 2.2 mmol) in DCM (40mL) was added a solution of NBS in 25 mL of DCM dropwise at rt. Thereaction mixture was stirred in the dark for 5 h. It was washed withwater (3×50 mL) and dried over MgSO₄ and concentrated. The crude productwas purified by silica chromatography (EtOAc/hexane) to afford6-bromo-9H-carbazol-2-yl acetate (WZ02025) as an off-white solid (250mg, containing 17% dibrominated product). MS (ESI) m/z 305 (M+H⁺).

Preparation of W138:

A suspension of 6-bromo-9H-carbazol-2-yl acetate (200 mg, 0.65 mmol) in30 mL MeOH and 4 mL of 1.0 M aqueous LiOH was stirred for 5 h. It wasneutralized with 1 M HCl and concentrated. The crude product waspurified by silica chromatography (EtOAc/hexane) to afford6-bromo-9H-carbazol-2-ol (W138) as an off-white solid (125 mg,containing 15% dibrominated product). ¹H NMR (400 MHz, acetone-d6) δ8.58 (s, 1H), 8.10 (d, J=2.0 Hz, 1 H), 1H), 7.92 (d, J=8.8 Hz, 1H), 7.42(dd, J=8.4, 2.0 Hz, 1H), 7.35 (s, 1H), 7.13 (d, J=8.4 Hz, 1H), 6.92 (d,J=2.0 Hz, 1H), 6.76 (dd, J=8.8, 2.0 Hz, 1H); MS (ESI) m/z 263 (M+H⁺).

Ex Vivo Competition Assay Using Amyloid (Ad Patient's Brain Slice)Autoradiography Staining

The carbazole series of AD imaging agents display surprisingly goodqualities when compared to previously established results performed byothers. Data from prior art suggests that compounds with higher LogPvalues have higher amyloid affinities, yet these same compounds can alsosuffer from high non-specific binding, i.e poor brain washout (J.Molecular Neuroscience 2003, 20, 255-260). For the disclosed studies inthis application, cLogP values were used in place of LogP values.

A study was conducted to examine the grey to white matter binding ratiosfor 4 different tracers: CB-001, CB-003, FDDNP and F-PiB (FIG. 7 andFIG. 8). A known carbazole containing imaging agent,18F-fluorocarazolol, was not examined in this study because of itsrelatively low cLogP value (2.77) compared to FDDNP and PiB, and itscompeting specific uptake into the beta-adrenoceptors. In addition,there is no prior art data suggesting that 18F-fluorocarazolol binds toAD plaques. After the human brain slices from AD patients were incubatedwith a given tracer for 30 min, the slices were washed with variousEtOH:water solutions in an attempt to optimize the grey to white matterratios (FIG. 9). The results were surprising and unexpected in view ofprevious work performed by other researchers. CB-001 has a slightlyhigher cLogP than FDDNP (3.8 vs 3.4) and would be expected to havepoorer washout than FDDNP based on these values. However, despite thedifference in cLogP values, CB-001 has a lower non-specific bindingpropensity and displays a much better grey to white matter ratiocompared to FDDNP (see section above, “original wash”). Morespecifically, the white matter binding of FDDNP is several shades darkerthan CB-001's white matter binding, indicating low non-specific bindingof CB-001. In contrast, F-PiB, which has a cLogP value of 3.99, alsodisplays reasonable, binding ratios similar to CB-001, albeit displayinga very weak overall signal. The washing data suggests that thecarbazoles are a viable and novel target for imaging AD-related targetsdue to their unique binding and washout properties.

To expand on these results, CB-003, a tracer with a cLogP value similarto FDDNP, was prepared and tested. Using washing conditions that werefar milder than the harsh washing conditions (FIG. 9), CB-003 displayedexcellent grey to white matter binding ratios that are far superior tothe results taken from FDDNP, PiB and CB-001. These favorable and uniqueresults suggest that CB-003 would have a more favorable brain washout inliving systems, leading to more specific uptake and lowered non-specificbinding, leading to a clear advantage over FDDNP and PiB imaging.

Summary of Washing Results:

Grey/white matter Grey/white binding ratio matter binding using harshratio using mild FDDNP wash wash Name Structure cLogP conditions*conditions** CB-001

3.789 Excellent Poor CB-003

3.4032 N/A Excellent FDDNP

3.422 Fair Poor PiB

3.9907 Poor (signal is washed away Poor *published FDDNP washconditions: 30 min incubation of CB-1 or CB-3 tracer, PBS wash (5 min),70% EtOH:water (1 min), 90% EtOH:water (1 min), 70% EtOH:water (1 min),PBS (5 min). The brain slices were 20 um thick. **mild wash conditions:30 min incubation of CB-1 or CB-3 tracer, PBS wash (5 min), 30%EtOH:water (2 min), 40% EtOH:water (2 min), 20% EtOH:water (2 min), PBS(5 min). The brain slices were 20 um thick.

The results demonstrate that 1) PiB blocks [18F]-CB001 staining withincreasing concentrations, suggesting the two compounds to compete forthe same amyloid binding pockets; 2) PiB appears to block tracer bindingwith the same strength as cold CB001, suggesting both to have similarbinding affinities; 3) FDDNP is much less capable of blocking[18F]-CB001 staining, due to its lower amyloid binding affinity.

This data suggests the following order of (non-specific) white matterbinding: FDDNP>CB001>[18F]-PiB >CB003

IC50 Determination with [18F]-PiB by ex vivo competition assay usingautoradiography staining Compound IC50 Average Code 1 2 3 4 5 6 7 8 9 1011 12 13 IC50 SD SD % F-PiB 43 43 40 50 55 41 45 6 13 PiB 80 40 40 48 6043 50 280 52 14 28 CB7 260 170 200 290 300 244 57 23 CB4 260 350 300 300400 322 54 17 CB12 610 300 450 390 438 130 30 CB24 540 540 CB1 1000 480740 368 50 CB10 900 900 CB3 1100 900 920 973 110 11

To further demonstrate the efficiency of employing these CB-relatedtracers as AD imaging agents, CB-003 was used to clearly differentiatebetween a healthy brain and an AD brain (FIG. 10). More specifically, byusing the mild wash protocol, the amyloid deposits were clearly visiblein the grey matter with little white matter uptake. The results werecorroborated by both antibody IHC and thioflaving T amyloid staining,confirming the specificity of uptake. These surprising resultsdemonstrate that this tracer possess the unique quality of rapid washoutfrom white matter and significant high uptake in grey matter that isspecific for AD plaques.

The carbazoles compete directly against 18F-PiB for the same bindingsites in human AD brains (FIG. 11). This surprising result could nothave been predicted given their dissimilar structures and CB-003's lackof a phenolic OH and terminal NH-Me group, which are deemed essentialfor binding to AD plaques. Despite CB-003 lacking both of thesefunctional groups, it still competes with 18F-PiB for binding sites inhuman AD brains. Because of the simplicity of its structure, thelabeling yields of CB-001 and CB-003 are exceptionally high and betterthan the labeling yields of 18F-PiB.

Surface Plasmon Resonance (SPR) Assay

An assay was developed using a Biacore instrument that introduced theligands over gold-surface immobilized target proteins and measured theresultant rates of association and disassociation in order to testvarious compounds that bind to soluble AD oligomers, polymers andfibrils (FIGS. 12 to 17).

The carbazole series also demonstrated a unique and surprising abilityto bind favorably and preferentially to insoluble aggregates (9 nM) oversoluble aggregates (262 nM) (FIG. 12 and FIG. 13). PiB also binds wellto insoluble aggregates (16 nM) but also binds essentially equally aswell to soluble aggregates (48 nM) (FIG. 14 and FIG. 15). For imagingapplications where it is favorable to distinguish between a tracer'sbinding to insoluble versus soluble aggregates, CB-003 provides a largerbinding ratio of 29:1, whereas PiB only provides a ratio 3:1. Thus,CB-003 may provide more selective binding information relative to PiB.The results indicate that 1) for soluble aggregate binding, PIB>CB3>CB4;and 2) for insoluble aggregate binding, PIB=CB3>CB4.

MicroPET Imaging with [18F]-CB-001 or [18F]-CB-003 in WT and App MICE

The results demonstrate that 1) WT and App mice show statisticallysignificant differences in tracer retention in the brain (FIG. 18A, FIG.18B and FIG. 19); 2) App mice show up to 25% larger brain/muscle ratioscompared to WT mice (FIG. 20 and FIG. 21). The carbazoles display both asurprising high uptake in mice brains (both WT and APP) and sufficientlyslow washout such that one can distinguish WT from APP mice (FIG. 22 andFIG. 23). Without being bound by any theory proposed herein, wespeculate that the reason behind these results may be that CB-003possesses a faster washout rate than 18F-PiB, which is consistent withconsistent with the staining data: 18F-PiB requires harsher washconditions in order to give reasonable grey to white matter ratios. Therapid washout of CB-003 is presumably a major factor for its lownon-specific binding, yet the washout is slow enough to distinguish WTfrom APP. This suggests that the carbazoles display a unique combinationof excellent washout and retention properties in human AD brains thatare not obvious from prior art data. CB-003, being a neutral compound,would also potentially possess greater uptake values versuszwitterionic-based imaging agents such as methylene blue.

1. A radiolabeled compound of the Formula Ito Formula VI:

wherein: For Formula I: A is N or CR¹; B is N or CR²; J is N or CR³; Kis N or CR⁴; L is N or CR⁵; M is N or CR⁶; P is N or CR⁷; and Q is N orCR⁸, provided that no more than two of A, B, J, K, L, M, P and Q can beN; X is a bond or is selected from the group consisting ofC₁₋₆alkylenyl, —C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—,—N(R¹⁰)C(S)—, —S(O)N(R¹⁰) and —N(R¹⁰)S(O)₂—; R¹, R², R³, R⁴, R⁵, R⁶, R⁷and R⁸ are each independently hydrogen or are each independentlyselected from the group consisting of amino, halo, cyano, nitro,hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀-arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; or at least one ofR¹ and R², R² and R³, R³ and R⁴, R⁵ and R⁶, R⁶ and R⁷, or R⁷ and R⁸together with the carbon atoms to which they are attached to, form asubstituted or unsubstituted aromatic or non-aromatic carbocyclic orheterocyclic ring; provided that at least any two of R¹, R², R³, R⁴, R⁵,R⁶, R⁷ and R⁸ are hydrogens; R⁹ is hydrogen or is selected from thegroup consisting of halo, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,halo-(CH₂CH₂)₁₋₆—; halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— and halo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—; eachR¹⁰ is independently H or C₁₋₆alkyl; provided that the compound ofFormula I is not a compound selected from the group consisting of2-fluoroethyl 6-fluoro-4-methoxy-9H-pyrido[3,4-b]indole-3-carboxylate,2-fluoropropyl 6-fluoro-4-methoxy-9H-pyrido[3,4-b]indole-3-carboxylate,9H-pyrido[3,4-b]indole-3-carboxylate,9H-pyrido[3,4-b]indole-3-thiocarboxylate,9H-pyrido[3,4-b]indole-3-carboxamide,9H-pyrido[3,4-b]indole-3-carbimidate, β-carboline-3-carboxylate,β-carboline-3-thiocarboxylate, β-carboline-3-carboxamide,β-carboline-3-carbimidate;(S)-4-(3-(3-(2′-18F]-fluoroethylamino)-2-hydroxypropoxy)-carbazol, R, S,SS and SR-1′-[18F]-fluorocarazolol (FCAR) and [11]C]-carazolol (CAR),(S)-(−)-4-(2-hydroxy-3-(1′-[18]fluoroisopropyl)-aminopropoxy)carbazole,7-(2-fluoroethoxy)-1-methyl-9H— β-carboline,7-(2-fluoropropoxy)-1-methyl-9H— β-carboline,7-[2-(2-fluoroethoxy)ethoxy]-1-methyl-9H— β-carboline,7-{2-[2-(2-fluoroethoxy)ethoxy]ethoxy}-1-methyl-9H-β-carboline andcarbazolyl-(4)-oxypropanolamine and their derivatives; wherein theradiolabel comprises a radionuclide selected from the group consistingof ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br; andpharmaceutically acceptable salts thereof; For Formula II: X is a bondor is selected from the group consisting of C₁₋₆alkylenyl, —C(O)—,—C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—, —S(O)N(R¹⁰)— and—N(R¹⁰)S(O)₂—; R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are each independentlyhydrogen or are each independently selected from the group consisting ofamino, halo, cyano, nitro, hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂,halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—, C₃₋₆cycloalkoxy,C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy,C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—,(C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₅alkylNR¹⁰C(O)—,C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—, C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— andC₆₋₁₀arylC(O)O—; or at least one of R¹ and R², R² and R³, R³ and R⁴, R⁵and R⁶, R⁶ and R⁷, or R⁷ and R⁸ together with the carbon atoms to whichthey are attached to, form a substituted or unsubstituted aromatic ornon-aromatic carbocyclic or heterocyclic ring; provided that at leastany two of R¹, R², R3, R⁴, R⁵, R⁶, R⁷ and R⁸ are hydrogens; R⁹ ishydrogen or is selected from the group consisting of halo, C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₆alkyl,heteroaryl, halo-(CH₂CH₂)₁₋₆—; halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— and halo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—; eachR¹⁰ is independently H or C₁₋₆alkyl; wherein the radiolabel comprises aradionuclide selected from the group consisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F,¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br; and pharmaceutically acceptable saltsthereof; For Formula III: Y and Y′ are each independently a bond or areeach independently selected from the group consisting of amino, halo,cyano, nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, haloC₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀ arylC₁₋₄alkoxy andheteroaryloxy when R¹¹ and R¹² are absent; R⁵, R⁶, R⁷ and R⁸ are eachindependently hydrogen or are each independently selected from the groupconsisting of amino, halo, cyano, nitro, hydroxyl, —SR¹⁰—C(O)NH₂,—C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—, C₃₋₆cycloalkoxy,C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy,C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—,(C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₅alkylNR¹⁰C(O)—,C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—, C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— andC₆₋₁₀arylC(O)O—; or at least one of R⁵ and R⁶, R⁶ and R⁷ or R⁷ and R⁸together with the carbon atoms to which they are attached to, form asubstituted or unsubstituted aromatic or non-aromatic carbocyclic orheterocyclic ring; provided that at least one of R⁵, R⁶, R⁷ and R⁸ is ahydrogen; each R¹⁰ is independently H or C₁₋₆alkyl; R¹¹ and R¹² are eachindependently absent, a hydrogen or are each independently selected fromthe group consisting of halo, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,halo-(CH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— and halo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—;wherein the radiolabel comprises a radionuclide selected from the groupconsisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br; andpharmaceutically acceptable salts thereof; For Formula IV: W is O or—N—X—R⁹; X is a bond or is selected from the group consisting ofC₁₋₆alkylenyl, —C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—,—N(R¹⁰)C(S)—, —S(O)N(R¹⁰) and —N(R¹⁰)S(O)₂—; Y and Y′ are eachindependently a bond or are each independently selected from the groupconsisting of amino, halo, cyano, nitro, hydroxyl, —SR¹⁰, —C(O)NH₂,—C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₆alkyl, heteroaryl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—, C₃₋₆cycloalkoxy,C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy,C₆₋₁₀arylC₁₋₄alkoxy and heteroaryloxy when R¹¹ and R¹² are absent; or Yis

and R¹² is absent; R¹, R², R³, and R⁴ are each independently hydrogen orare each independently selected from the group consisting of amino,halo, cyano, nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; or at least one ofR⁵ and R⁶, R⁶ and R⁷ or R⁷ and R⁸ together with the carbon atoms towhich they are attached to, form a substituted or unsubstituted aromaticor non-aromatic carbocyclic or heterocyclic ring; provided that at leastone of R¹, R², R³ and R⁴ is a hydrogen; R⁵, R⁶, R⁷, R⁸ and R^(o) areeach independently hydrogen or are each independently selected from thegroup consisting of amino, halo, cyano, nitro, hydroxyl, —SR¹⁰,—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl perhaloC₁₋₆alkyl C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl,heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—,C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkyl C₁₋₅alkoxy, heteroarylC₂₋₅alkoxy,C₆₋₁₄aryloxy, C₆₋₁₀-arylC₁₋₄alkoxy, heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—,(C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₅alkylNR¹⁰C(O)—,C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—, C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— andC₆₋₁₀arylC(O)O—; R⁹ is hydrogen or is selected from the group consistingof halo, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, halo-(CH₂CH₂)₁₋₆—;halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— andhalo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—; each R¹⁰ is independently H or C₁₋₆alkyl;R¹¹ and R¹² are each independently absent, a hydrogen or are eachindependently selected from the group consisting of halo, C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl,heteroaryl, halo-(CH₂CH₂)₁₋₆—; halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— and halo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—;wherein the radiolabel comprises a radionuclide selected from the groupconsisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br; andpharmaceutically acceptable salts thereof; For Formula V: X is a bond oris selected from the group consisting of C₁₋₆alkylenyl, —C(O)—, —C(S)—,—C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—, —S(O)N(R¹⁰)— and—N(R¹⁰)S(O)₂—; R⁵ and R⁶ are each independently hydrogen or are eachindependently selected from the group consisting of amino, halo, cyano,nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₂₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; or R⁵ and R⁶together with the carbon atoms to which they are attached to, form asubstituted or unsubstituted aromatic or non-aromatic carbocyclic orheterocyclic ring; R⁹ is hydrogen or is selected from the groupconsisting of halo, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₀aryl, C₆₋₁₀-arylC₁₋₄alkyl, heteroaryl, halo-(CH₂CH₂)₁₋₆—;halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— andhalo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—; each R¹⁰ is independently H or C₁₋₆alkyl;wherein the radiolabel comprises a radionuclide selected from the groupconsisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br; andpharmaceutically acceptable salts thereof; For Formula VI: X is a bondor is selected from the group consisting of C₁₋₆alkylenyl, —C(O)—,—C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—, —S(O)N(R¹⁰)— and—N(R¹⁰)S(O)₂—; Y is a bond or is selected from the group consisting ofamino, halo, cyano, nitro, hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂,halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—, C₃₋₆cycloalkoxy,C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy,C₆₋₁₀arylC₁₋₄alkoxy and heteroaryloxy; R⁵ and R⁶ are each independentlyhydrogen or are each independently selected from the group consisting ofamino, halo, cyano, nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂,haloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; or R⁵ and R⁶together with the carbon atoms to which they are attached to, form asubstituted or unsubstituted aromatic or non-aromatic carbocyclic orheterocyclic ring; R⁹ is hydrogen or is selected from the groupconsisting of halo, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, halo-(CH₂CH₂)₁₋₆—;halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— andhalo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—; each R¹⁰ is independently H or C₁₋₆alkyl;R¹¹ is a hydrogen or is selected from the group consisting of halo,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, halo-(CH₂CH₂)₁₋₆—;halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— andhalo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—; provided that at least one of R¹ to R¹²comprises a radiolabel, as defined herein; wherein the radiolabelcomprises a radionuclide selected from the group consisting of ¹¹C, ¹³N,¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br; and pharmaceuticallyacceptable salts thereof.
 2. The radiolabeled compound of claim 1,wherein: For Formula I: A is N or CR¹; B is N or CR²; J is N or CR³; Kis N or CR⁴; L is N or CR⁵; M is N or CR⁶; P is N; and Q is N or CR⁸; Xis a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O— and —C(S)O—; and R¹, R², R³, R⁴, R⁵, R⁶, R⁷ andR⁸ are each independently hydrogen or are each independently selectedfrom the group consisting of amino, halo, cyano, nitro, hydroxyl, —SR¹⁰,—C(O)NH₂, —C(S)NH₂, haloC₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl,heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—,C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy,C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—,(C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₅alkylNR¹⁰C(O)—,C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—, C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— andC₆₋₁₀arylC(O)O—; or at least one of R¹ and R², R² and R³, R³ and R⁴, R⁵and R⁶, R⁶ and R⁷, or R⁷ and R⁸ together with the carbon atoms to whichthey are attached to, form a substituted or unsubstituted aromatic ornon-aromatic carbocyclic or heterocyclic ring; For Formula II: X is abond or is selected from the group consisting of C₁₋₆alkylenyl, —C(O)—,—C(S)—, —C(O)O— and —C(S)O—; and R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ areeach independently hydrogen or are each independently selected from thegroup consisting of amino, halo, cyano, nitro, hydroxyl, —SR¹⁰,—C(O)NH₂, —C(S)NH₂, haloC₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl,heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—,C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy,C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—,(C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₅alkylNR¹⁰C(O)—,C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—, C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— andC₆₋₁₀arylC(O)O—; or at least one of R¹ and R², R² and R³, R³ and R⁴, R⁵and R⁶, R⁶ and R⁷, or R⁷ and R⁸ together with the carbon atoms to whichthey are attached to, form a substituted or unsubstituted aromatic ornon-aromatic carbocyclic or heterocyclic ring; For Formula III: Y and Y′are each independently selected from the group consisting of amino,halo, cyano, nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy andheteroaryloxy when R¹¹ and R¹² are absent; R⁵, R⁶, R⁷ and R⁸ are eachindependently hydrogen or are each independently selected from the groupconsisting of amino, halo, cyano, nitro, hydroxyl, —SR¹⁰, —C(O)NH₂,—C(S)NH₂, haloC₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₂₋₅alkoxy,halo-C₂₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—, C₃₋₆cycloalkoxy,C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy,C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—,(C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-, halo-C₂₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₅alkylNR¹⁰C(O) —,C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—, C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— andC₆₋₁₀arylC(O)O—; or at least one of R¹ and R², R² and R³, R³ and R⁴, R⁵and R⁶, R⁶ and R⁷, or R⁷ and R⁸ together with the carbon atoms to whichthey are attached to, form a substituted or unsubstituted aromatic ornon-aromatic carbocyclic or heterocyclic ring; For Formula IV: W is O or—N—X—R⁹; R¹, R², R³ and R⁴ are each independently hydrogen or are eachindependently selected from the group consisting of amino, halo, cyano,nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; or at least one ofR¹ and R², R² and R³ or R³ and R⁴ together with the carbon atoms towhich they are attached to, form a substituted or unsubstituted aromaticor non-aromatic carbocyclic or heterocyclic ring; For Formula V: X is abond or is selected from the group consisting of C₁₋₆alkylenyl, —C(O)—,—C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—, —S(O)N(R¹⁰) and—N(R¹⁰)S(O)₂—; R⁵ and R⁶ are each independently hydrogen or are eachindependently selected from the group consisting of amino, halo, cyano,nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; and R⁹ is hydrogenor is selected from the group consisting of halo, C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl,heteroaryl, halo-(CH₂CH₂)₁₋₆—; halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— and halo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—; ForFormula VI: X is a bond or is selected from the group consisting ofC₁₋₆alkylenyl, —C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—,—N(R¹⁰)C(S)—, —S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—; Y is a bond or is selectedfrom the group consisting of amino, halo, cyano, nitro, hydroxyl, —SR¹⁰,—C(O)NH₂, —C(S)NH₂, haloC₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl,heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—,C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy,C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy and heteroaryloxy; R⁵ and R⁶ are eachindependently hydrogen or are each independently selected from the groupconsisting of amino, halo, cyano, nitro, hydroxyl, —SR¹⁰, —C(O)NH₂,—C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—, C₃₋₆cycloalkoxy,C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy,C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—,(C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₅alkylNR¹⁰C(O)—,C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—, C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— andC₆₋₁₀arylC(O)O—; R⁹ is hydrogen or is selected from the group consistingof halo, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, halo-(CH₂CH₂)₁₋₆—;halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— andhalo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—; and R¹¹ is absent, a hydrogen or isselected from the group consisting of halo, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,halo-(CH₂CH₂)₁₋₆—; halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— and halo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—;wherein the radiolabel comprises a radionuclide selected from the groupconsisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br; andpharmaceutically acceptable salts thereof.
 3. The compound of claim 2,wherein: For Formula I: A is N or CR¹; B is N or CR²; J is N or CR³; Kis N or CR⁴; L is N or CR⁵; M is N or CR⁶; P is N or CR⁷; and Q is N orCR⁸, provided that no more than two of A, B, J, K, L, M, P and Q can beN; X is a bond or is selected from the group consisting ofC₁₋₆alkylenyl, —C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—,—N(R¹⁰)C(S)—, —S(O)N(R¹⁰) and —N(R¹⁰)S(O)₂—; and R¹, R², R³, R⁴, R⁵, R⁶,R⁷ and R⁸ are each independently hydrogen or are each independentlyselected from the group consisting of amino, halo, cyano, nitro,hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O— and C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—; For Formula II:X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰) and —N(R¹⁰)S(O)₂—; and R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ areeach independently hydrogen or are each independently selected from thegroup consisting of amino, halo, cyano, nitro, hydroxyl, —SR¹⁰,—C(O)NH₂, —C(S)NH₂, haloC₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, heteroarylC₂₋₅alkoxy,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—and C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—; For Formula III: Y and Y′ are eachindependently a bond or are each independently selected from the groupconsisting of amino, halo, cyano, nitro, hydroxyl, —SR¹⁰—C(O)NH₂,—C(S)NH₂, haloC₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—, C₃₋₆cycloalkoxy,C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy,C₆₋₁₀arylC₁₋₄alkoxy and heteroaryloxy when R¹¹ and R¹² are absent; andR⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or are eachindependently selected from the group consisting of amino, halo, cyano,nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryl, C₆₋₁₀-arylC₁₋₄alkyl, heteroaryl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O— and C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—; For Formula IV:W is O or —N—X—R⁹; X is a bond or is selected from the group consistingof C₁₋₆alkylenyl, —C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—,—N(R¹⁰)C(S)—, —S(O)N(R¹⁰) and —N(R¹⁰)S(O)₂—; Y and Y′ are eachindependently a bond or are each independently selected from the groupconsisting of amino, halo, cyano, nitro, hydroxyl, —SR¹⁰—C(O)NH₂,—C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC heteroaryl, C₁₋₅alkoxy,H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—, C₃₋₆cycloalkoxy,C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy,C₆₋₁₀arylC₁₋₄alkoxy and heteroaryloxy when R¹¹ and R¹² are absent; andR¹, R², R³ and R⁴ are each independently hydrogen or are eachindependently selected from the group consisting of amino, halo, cyano,nitro, hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O— and C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—; For Formula V:X is a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—; and R⁵ and R⁶ are each independentlyhydrogen or are each independently selected from the group consisting ofamino, halo, cyano, nitro, hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂,halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, heteroarylC₂₋₅alkoxy, C₆₋₁₄aryl,C₆₋₁₀-arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O— andC₁₋₃alkyl(OCH₂CH₂)₁₋₆O—; For Formula VI: X is a bond or is selected fromthe group consisting of C₁₋₆alkylenyl, —C(O)—, —C(S)—, —C(O)O—, —C(S)O—,—N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—, —S(O)N(R¹⁰) and —N(R¹⁰)S(O)₂—; Y is a bondor is selected from the group consisting of amino, halo, cyano, nitro,hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂, haloC₁₋₆alkyl, perhaloC₁₋₆alkyl,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy andheteroaryloxy when R¹¹ is absent; and R⁵ and R⁶ are each independentlyhydrogen or are each independently selected from the group consisting ofamino, halo, cyano, nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂,halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, heteroarylC₂₋₅alkoxy, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O— andC₁₋₃alkyl(OCH₂CH₂)₁₋₆O—; wherein the radiolabel comprises a radionuclideselected from the group consisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I,¹²⁵I, ¹³¹I and ⁷⁷Br; and pharmaceutically acceptable salts thereof. 4.The compound of claim 1, wherein: For Formula I: A is N or CR¹; B is Nor CR²; J is N or CR³; K is N or CR⁴; L is N or CR⁵; M is N or CR⁶; P isN or CR⁷; and Q is N or CR⁸, provided that no more than two of A, B, J,K, L, M, P and Q can be N; X is a bond or is selected from the groupconsisting of C₁₋₆alkylenyl, —C(O)—, —C(S)—, —C(O)O—, —C(S)O—,—N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—, —S(O)N(R¹⁰) and —N(R¹⁰)S(O)₂—; and R¹, R²,R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or are eachindependently selected from the group consisting of halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-and halo-C₁₋₅alkylNR¹⁰C(O)—; For Formula II: X is a bond or is selectedfrom the group consisting of C₁₋₆alkylenyl, —C(O)—, —C(S)—, —C(O)O—,—C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—, —S(O)N(R¹⁰) and —N(R¹⁰)S(O)₂—; andR¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or areeach independently selected from the group consisting ofhalo-C₂₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O—, halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)- and halo-C₁₋₅alkylNR¹⁰C(O)—; ForFormula III: Y and Y′ are each independently a bond or are eachindependently selected from the group consisting of amino, halo, cyano,nitro, hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂, haloC₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy andheteroaryloxy when R¹¹ and R¹² are absent; and R⁵, R⁶, R⁷ and R⁸ areeach independently hydrogen or are each independently selected from thegroup consisting of halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, FCH₂CH₂—(OCH₂CH₂)₁₋₆O—,haloC₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-and halo-C₁₋₅alkylNR¹⁰C(O)—; For Formula IV: W is O or —N—X—R⁹; X is abond or is selected from the group consisting of C₁₋₆alkylenyl, —C(O)—,—C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—, —S(O)N(R¹⁰)— and—N(R¹⁰)S(O)₂—; Y and Y′ are each independently a bond or are eachindependently selected from the group consisting of amino, halo, cyano,nitro, hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂, halo-C₂₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy andheteroaryloxy when R¹¹ and R¹² are absent; and R¹, R², R³ and R⁴ areeach independently hydrogen or are each independently selected from thegroup consisting of halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)- and halo-C₁₋₅alkylNR¹⁰C(O)—; ForFormula V: X is a bond or is selected from the group consisting ofC₁₋₆alkylenyl, —C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—,—N(R¹⁰)C(S)—, —S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—; and R⁵ and R⁶ are eachindependently hydrogen or are each independently selected from the groupconsisting of halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)- and halo-C₁₋₅alkylNR¹⁰C(O)—; ForFormula VI: X is a bond or is selected from the group consisting ofC₁₋₆alkylenyl, —C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—,—N(R¹⁰)C(S)—, —S(O)N(R¹⁰) and —N(R¹⁰)S(O)₂—; Y is a bond or is selectedfrom the group consisting of amino, halo, cyano, nitro, hydroxyl,—SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl,heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—,C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy,C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy and heteroaryloxy when R^(H) isabsent; and R⁵ and R⁶ are each independently hydrogen or are eachindependently selected from the group consisting of halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O—,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-and halo-C₁₋₅alkylNR¹⁰C(O)—; wherein the radiolabel comprises aradionuclide selected from the group consisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F,¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br; and pharmaceutically acceptable saltsthereof.
 5. The compound of claim 1, wherein: For Formula I: A is N orCR¹; B is N or CR²; J is N or CR³; K is N or CR⁴; L is N or CR⁵; M is Nor CR⁶; P is N or CR⁷; and Q is N or CR⁸, provided that no more than twoof A, B, J, K, L, M, P and Q can be N; X is a bond or is selected fromthe group consisting of C₁₋₆alkylenyl, —C(O)—, —C(S)—, —C(O)O—, —C(S)O—,—N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—, —S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—; and R¹, R²,R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or are eachindependently selected from the group consisting of C₃₋₆cycloalkoxy,C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy,C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—,(C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; For Formula II: Xis a bond or is selected from the group consisting of C₁₋₆alkylenyl,—C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—,—S(O)N(R¹⁰) and —N(R¹⁰)S(O)₂—; and R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ areeach independently hydrogen or are each independently selected from thegroup consisting of C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—, C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— andC₆₋₁₀arylC(O)O—; For Formula III: Y and Y′ are each independently a bondor are each independently selected from the group consisting of amino,halo, cyano, nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, haloC₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₂₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀-arylC₁₋₄alkoxy andheteroaryloxy when R¹¹ and R¹² are absent; and R⁵, R⁶, R⁷ and R⁸ areeach independently hydrogen or are each independently selected from thegroup consisting of C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—, C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— andC₆₋₁₀arylC(O)O—; For Formula IV: W is O or —N—X—R⁹; X is a bond or isselected from the group consisting of C₁₋₆alkylenyl, —C(O)—, —C(S)—,—C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—, —S(O)N(R¹⁰)— and—N(R¹⁰)S(O)₂—; Y and Y′ are each independently a bond or are eachindependently selected from the group consisting of amino, halo, cyano,nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₂₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy andheteroaryloxy when R¹¹ and R¹² are absent; and R¹, R², R³ and R⁴ areeach independently hydrogen or are each independently selected from thegroup consisting of C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀-arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—, C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— andC₆₋₁₀arylC(O)O—; For Formula V: X is a bond or is selected from thegroup consisting of C₁₋₆alkylenyl, —C(O)—, —C(O)O—, —C(S)O—,—N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—, —S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—; and R⁵ andR⁶ are each independently hydrogen or are each independently selectedfrom the group consisting of C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—, C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— andC₆₋₁₀arylC(O)O—; For Formula VI: X is a bond or is selected from thegroup consisting of C₁₋₆alkylenyl, —C(O)—, —C(S)—, —C(O)O—, —C(S)O—,—N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—, —S(O)N(R¹⁰— and —N(R¹⁰)S(O)₂—; Y is a bondor is selected from the group consisting of amino, halo, cyano, nitro,hydroxyl, —C(O)NH₂, —C(S)NH₂, halo-C₂₋₆alkyl, perhaloC₁₋₆alkyl,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy andheteroaryloxy when R¹¹ is absent; and R⁵ and R⁶ are each independentlyhydrogen or are each independently selected from the group consisting ofC₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy,C₆₋₁₄aryloxy, C₆₋₁₀-arylC₁₋₄alkoxy, heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—,(C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; wherein theradiolabel comprises a radionuclide selected from the group consistingof ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br; andpharmaceutically acceptable salts thereof.
 6. The radiolabeled compoundof claim 1 wherein: For Formula I and Formula II: X is a bond or isselected from the group consisting of C₁₋₆alkylenyl, —C(O)—, —C(S)—,—C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—, —S(O)N(R¹⁰) and—N(R¹⁰)S(O)₂—; R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are each independentlyhydrogen or are each independently selected from the group consisting ofamino, halo, cyano, nitro, hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂,halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—, C₃₋₆cycloalkoxy,C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy,C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—,(C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₅alkylNR¹⁰C(O)—,C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—, C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— andC₆₋₁₀arylC(O)O—; or at least one of R¹ and R², R² and R³, R³ and R⁴, R⁵and R⁶, R⁶ and R⁷, or R⁷ and R⁸ together with the carbon atoms to whichthey are attached to, form a substituted or unsubstituted aromatic ornon-aromatic carbocyclic or heterocyclic ring; provided that at leastany two of R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are hydrogens; R⁹ ishydrogen or is selected from the group consisting of halo, C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl,heteroaryl, halo(CH₂CH₂)₁₋₆—; haloCH₂CH₂—(OCH₂CH₂)₁₋₆—,haloCH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— and haloCH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—; and eachR¹⁰ is independently H or C₁₋₆alkyl; For Formula III: Y and Y′ are eachindependently a bond or are each independently selected from the groupconsisting of amino, halo, cyano, nitro, hydroxyl, —SR¹⁰, —C(O)NH₂,—C(S)NH₂, haloC₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—, C₃₋₆cycloalkoxy,C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy,C₆₋₁₀arylC₁₋₄alkoxy and heteroaryloxy when R¹¹ and R¹² are absent; andR⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or are eachindependently selected from the group consisting of amino, halo, cyano,nitro, hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,haloC₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, haloC₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; or at least one ofR¹ and R², R² and R³, R³ and R⁴, R⁵ and R⁶, R⁶ and R⁷, or R⁷ and R⁸together with the carbon atoms to which they are attached to, form asubstituted or unsubstituted aromatic or non-aromatic carbocyclic orheterocyclic ring; provided that at least any two of R⁵, R⁶, R⁷ and R⁸are hydrogens; R⁹ is hydrogen or is selected from the group consistingof halo, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, halo(CH₂CH₂)₁₋₆—;halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— andhalo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—; and each R¹⁰ is independently H orC₁₋₆alkyl; For Formula IV: W is O or —N—X—R⁹; X is a bond or is selectedfrom the group consisting of C₁₋₆alkylenyl, —C(O)—, —C(S)—, —C(O)O—,—C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—, —S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—; Yand Y′ are each independently a bond or are each independently selectedfrom the group consisting of amino, halo, cyano, nitro, hydroxyl,—SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₇cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl,heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—,C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy,C₆₋₁₄aryloxy; C₆₋₁₀-arylC₁₋₄alkoxy and heteroaryloxy when R¹¹ and R¹²are absent; and R¹, R², R³ and R⁴ are each independently hydrogen or areeach independently selected from the group consisting of amino, halo,cyano, nitro, hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,haloC₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, haloC₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,haloC₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; or at least one ofR¹ and R², R² and R³ or R³ and R⁴ together with the carbon atoms towhich they are attached to, form a substituted or unsubstituted aromaticor non-aromatic carbocyclic or heterocyclic ring; provided that at leastany two of R¹, R², R³ and R⁴ are hydrogens; R⁹ is hydrogen or isselected from the group consisting of halo, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,halo-(CH₂CH₂)₁₋₆—; halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— and halo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—; andeach R¹⁰ is independently H or C₁₋₆alkyl; For Formula V: X is a bond oris selected from the group consisting of C₁₋₆alkylenyl, —C(O)—, —C(S)—,—C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—, —N(R¹⁹)C(S)—, —S(O)N(R¹⁰)— and—N(R¹⁰)S(O)₂—; and R⁵ and R⁶ are each independently each independentlyhydrogen or are each independently selected from the group consisting ofamino, halo, cyano, nitro, hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂,halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—, C₃₋₆cycloalkoxy,C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy,C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—,(C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-,haloC₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₅alkylNR¹⁰C(O)—,C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—, C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— andC₆₋₁₀arylC(O)O—; R⁹ is hydrogen or is selected from the group consistingof halo, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, halo-(CH₂CH₂)₁₋₆—;halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— andhalo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—; and each R¹⁰ is independently H orC₁₋₆alkyl; For Formula VI: X is a bond or is selected from the groupconsisting of C₁₋₆alkylenyl, —C(O)—, —C(S)—, —C(O)O—, —C(S)O—,—N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—, —S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—; Y is a bondor is selected from the group consisting of amino, halo, cyano, nitro,hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, haloC₁₋₆alkyl, perhaloC₁₋₆alkyl,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₂₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy andheteroaryloxy when R¹¹ is absent; and R⁵ and R⁶ are each independentlyeach independently hydrogen or are each independently selected from thegroup consisting of amino, halo, cyano, nitro, hydroxyl, —SR¹⁰,—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl,heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—,C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy,C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—,(C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylNR¹⁰C, (O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₅alkylNR¹⁰C(O)—,C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—, C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— andC₆₋₁₀arylC(O)O—; R⁹ is hydrogen or is selected from the group consistingof halo, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, halo-(CH₂CH₂)₁₋₆—;halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— andhalo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—; and each R¹⁰ is independently H orC₁₋₆alkyl; wherein the radiolabel comprises a radionuclide selected fromthe group consisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and⁷⁷Br; and pharmaceutically acceptable salts thereof.
 7. The compound ofclaim 6, wherein: For Formula I and Formula II: R¹, R², R³, R⁴, R⁵, R⁶,R⁷ and R⁸ are each independently hydrogen or are each independentlyselected from the group consisting of amino, halo, cyano, nitro,hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O— andC₁₋₃alkyl(OCH₂CH₂)₁₋₆O—; For Formula III: R⁵, R⁶, R⁷ and R⁸ are eachindependently hydrogen or are each independently selected from the groupconsisting of amino, halo, cyano, nitro, hydroxyl, —SR¹⁰, —C(O)NH₂,—C(S)NH₂, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O— and C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—; ForFormula IV: R¹, R², R³ and R⁴ are each independently hydrogen or areeach independently selected from the group consisting of amino, halo,cyano, nitro, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, C₁₋₅alkoxy,H(OCH₂CH₂)₁₋₆O— and C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—. For Formula V and FormulaVI: R⁵ and R⁶ are each independently hydrogen or are each independentlyselected from the group consisting of amino, halo, cyano, nitro,hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O— andC₁₋₃alkyl(OCH₂CH₂)₁₋₆O—. wherein the radiolabel comprises a radionuclideselected from the group consisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I,¹²⁵I, ¹³¹I and ⁷⁷Br; and pharmaceutically acceptable salts thereof. 8.The compound of claim 1, wherein the halo-moiety of the group selectedfrom halo-C₁₋₆alkyl, halo-C₂₋₅alkoxy, halo-C₂₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O—, halo-(CH₂CH₂)₁₋₆—;halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)—,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—, halo-C₂₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-,halo-C₂₋₆alkylOC(O)CH(C₁₋₅alkyl)- and haloC₁₋₅alkylNR¹⁰C(O)— is selectedfrom the group consisting of fluoro, iodo and bromo.
 9. The compound ofclaim 6, wherein: For Formula I and Formula II: R¹, R², R³, R⁴, R⁵, R⁶,R⁷ and R⁸ are each independently hydrogen or are each independentlyselected from the group consisting of halo-C₂₋₅alkoxy, haloC₁₋₆alkyl,perhaloC₁₋₆alkyl, halo-C₂₋₃alkyl(OCH₂CH₂)₁₋₆O—, F—CH₂CH₂O—,F—CH₂CH₂—(OCH₂CH₂)₁₋₆O—, haloC₂₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-,haloC₂₋₆alkylOC(O)CH(C₁₋₅alkyl)- and haloC₂₋₅alkylNR¹⁰C(O)—; For FormulaIII: R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or are eachindependently selected from the group consisting of halo-C₁₋₅alkoxy,haloC₁₋₆alkyl, perhaloC₁₋₆alkyl, halo-C₂₋₃alkyl(OCH₂CH₂)₁₋₆O—,F—CH₂CH₂O—, F—CH₂CH₂—(OCH₂CH₂)₁₋₆O—,haloC₂₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, haloC₂₋₆alkylOC(O)CH(C₁₋₅alkyl)-and haloC₂₋₅alkylNR¹⁰C(O)—; For Formula IV: R¹, R², R³ and R⁴ are eachindependently hydrogen or are each independently selected from the groupconsisting of halo-C₁₋₅alkoxy, haloC₁₋₆alkyl, perhaloC₁₋₆alkyl,halo-C₂₋₃alkyl(OCH₂CH₂)₁₋₆O—, F—CH₂CH₂O—, F—CH₂CH₂—(OCH₂CH₂)₁₋₆O—,haloC₂₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, haloC₂₋₆alkylOC(O)CH(C₁₋₅alkyl)-and haloC₂₋₅alkylNR¹⁰C(O)—; For Formula V and Formula VI: R⁵ and R⁶ areeach independently hydrogen or are each independently selected from thegroup consisting of halo-C₁₋₅alkoxy, haloC₁₋₆alkyl, perhaloC₁₋₆alkyl,halo-C₂₋₃alkyl(OCH₂CH₂)₁₋₆O—, F—CH₂CH₂O—, F—CH₂CH₂—(OCH₂CH₂)₁₋₆O—,haloC₂₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, haloC₂₋₆alkylOC(O)CH(C₁₋₅alkyl)-and haloC₂₋₅alkylNR¹⁰C(O)—; wherein the radiolabel comprises aradionuclide selected from the group consisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F,¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br; and pharmaceutically acceptable saltsthereof.
 10. The compound of claim 6, wherein: For Formula I and FormulaII: R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen orare each independently selected from the group consisting of C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, heteroarylC₂₋₅alkoxy,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₃₋₆cycloalkoxy,C₃₋₁₂cycloalkylC₁₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy,heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—, C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— andC₆₋₁₀arylC(O)O—; For Formula III: R⁵, R⁶, R⁷ and R⁸ are eachindependently hydrogen or are each independently selected from the groupconsisting of C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy, C₆₋₁₄aryloxy,C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—,(C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; For Formula IV: R¹,R², R³ and R⁴ are each independently hydrogen or are each independentlyselected from the group consisting of C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, heteroarylC₂₋₅alkoxy, C₆₋₁₄aryl, heteroaryl,C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy, C₆₋₁₄aryloxy,C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—,(C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; For Formula V andFormula VI: R⁵ and R⁶ are each independently hydrogen or are eachindependently selected from the group consisting of C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, heteroarylC₂₋₅alkoxy,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₃₋₆cycloalkoxy,C₃₋₁₂cycloalkylC₁₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy,heteroaryloxy, C₁₋₅alkylNR¹⁰C(O) —, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—, C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— andC₆₋₁₀arylC(O)O—; wherein the radiolabel comprises a radionuclideselected from the group consisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I,¹²⁵I, ¹³¹I and ⁷⁷Br; and pharmaceutically acceptable salts thereof. 11.The compound of claim 6, wherein: For Formula I and Formula II: R¹, R²,R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or selectedfrom the group consisting of F—C₁₋₆alkyl, F—C₁₋₅alkoxy,F—C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, F—CH₂CH₂O—, F—CH₂CH₂—(OCH₂CH₂)₁₋₆O—,4-(F—C₁₋₆alkyl)-1H-1,2,3-triazol-1-yl-(C₂₋₅alkoxy),F—C₂₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, F—C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)- andF—C₁₋₅alkylNR¹⁰C(O)—; For Formula III: R⁵, R⁶, R⁷ and R⁸ are eachindependently hydrogen or selected from the group consisting ofF—C₁₋₆alkyl, F—C₁₋₅alkoxy, F—C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, F—CH₂CH₂O—,F—CH₂CH₂—(OCH₂CH₂)₁₋₆O—,4-(F—C₁₋₆alkyl)-1H-1,2,3-triazol-1-yl-(C₂₋₅alkoxy),F—C₂₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl), F—C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)- andF—C₁₋₅alkylNR¹⁰C(O)—; For Formula IV: R¹, R², R³ and R⁴ are eachindependently hydrogen or selected from the group consisting ofF—C₁₋₆alkyl, F—C₁₋₅alkoxy, F—C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, F—CH₂CH₂O—,F—CH₂CH₂—(OCH₂CH₂)₁₋₆O—,4-(F—C₁₋₆alkyl)-1H-1,2,3-triazol-1-yl-(C₂₋₅alkoxy),F—C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, F—C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)- andF—C₁₋₅alkylNR¹⁰C(O)—; For Formula V and Formula VI: R⁵ and R⁶ are eachindependently hydrogen or selected from the group consisting ofF—C₁₋₆alkyl, F—C₁₋₅alkoxy, F—C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, F—CH₂CH₂O—,F—CH₂CH₂—(OCH₂CH₂)₁₋₆O—,4-(F—C₁₋₆alkyl)-1H-1,2,3-triazol-1-yl-(C₂₋₅alkoxy),F—C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, F—C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)- andF—C₁₋₅alkylNR¹⁰C(O)—; wherein the radiolabel comprises a radionuclideselected from the group consisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I,¹²⁵I, ¹³¹I and ⁷⁷Br; and pharmaceutically acceptable salts thereof. 12.The compound of claim 6, wherein: For Formula I and Formula II: at leastfour of R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are hydrogens; For FormulaIII: at least two of R⁵, R⁶, R⁷ and R⁸ are hydrogens; For Formula IV: atleast two of R¹, R², R³ and R⁴ are hydrogens; For Formula V and FormulaVI: at least one of R⁵ or R⁶ is a hydrogen; wherein the radiolabelcomprises a radionuclide selected from the group consisting of ¹¹C, ¹³N,¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br; and pharmaceuticallyacceptable salts thereof.
 13. The compound of claim 1, wherein the aminogroup is selected from the group consisting of NH₂—, CH₃NH—, (CH₃)₂N—,F—(C₂₋₃-alkylO)₁₋₄-alkyl-NH—, (C₁₋₃-alkyl)₂N—, (C₁₋₆alkyl)₂N—,C₃₋₆cycloalkylNH—, (C₃₋₆cycloalkyl)₂N—, C₃₋₁₂cycloalkylC₁₋₅alkylNH—,C₆₋₁₄arylNH—, C₆₋₁₀arylC₁₋₄alkylNH—, heteroarylNH—, C₆₋₁₄aryloxyNH—,C₆₋₁₀arylC₁₋₄alkoxyNH— and heteroaryloxyNH—.
 14. The compound of claim 1of the Formula I, II, V and VI, wherein X is a bond and R⁹ is hydrogen.15. The compound of claim 1, wherein the compound comprises at least oneradionuclide selected from the group consisting of ¹¹C, ¹⁵O, ¹⁸F, ¹²³I,¹²⁵I, ¹³¹I and ⁷⁷Br.
 16. The radiolabeled compound of claim 1 that is:2-(2-fluoroethoxy)-9H-carbazole; 9-(2-fluoroethyl)-9H-carbazol-2-ol;N-(2-fluoroethyl)-7-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-9H-carbazol-3-amine;7-(2-fluoroethoxy)-N,N-dimethyl-9H-carbazol-2-amine;7-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-N-methyl-9H-carbazol-3-amine;1-(3,6-diamino-9H-carbazol-9-yl)-3-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)propan-1-one;N-(2-fluoroethyl)-2-hydroxy-11H-benzo[a]carbazole-3-carboxamide;2-(6-chloro-9H-carbazol-2-yl)-N-(2-fluoroethyppropanamide;2-(6-fluoro-9H-carbazol-2-yl)-N,N-dimethylpropanamide;2-methoxy-9H-carbazole; 6-iodo-2-methoxy-9H-carbazole;2-(2-fluoroethoxy)-9H-carbazole; 9-(2-fluoroethyl)-9H-carbazol-2-ol;N-(2-fluoroethyl)-7-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-9H-carbazol-3-amine;7-(2-fluoroethoxy)-N,N-dimethyl-9H-carbazol-2-amine;7-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-N-methyl-9H-carbazol-3-amine;1-(3,6-diamino-9H-carbazol-9-yl)-3-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)propan-1-one;N-(2-fluoroethyl)-2-hydroxy-11H-benzo[a]carbazole-3-carboxamide;2-(6-chloro-9H-carbazol-2-yl)-N-(2-fluoroethyl)propanamide; and2-(6-fluoro-9H-carbazol-2-yl)-N,N-dimethylpropanamide.
 17. Aradiolabeled compound of the formula IIa:

wherein: X is a bond or is selected from the group consisting ofC₁₋₆alkylenyl, —C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—,—N(R¹⁰)C(S)—, —S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂; R², R³, R⁴, R⁶, R⁷ and R⁸are each independently hydrogen or are each independently selected fromthe group consisting of amino, halo, cyano, nitro, hydroxyl,—SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl,heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; provided that atleast any two of R², R³, R⁴, R⁶, R⁷ and R⁸ are hydrogens, and at leastone of R², R³, R⁴, R⁶, R⁷, R⁸ and R⁹ comprises the radiolabel; R⁹ ishydrogen or is selected from the group consisting of halo, C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl,heteroaryl, halo-(CH₂CH₂)₁₋₆—; halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— and halo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—; eachR¹⁰ is independently H or C₁₋₆alkyl; wherein the radiolabel comprises aradionuclide selected from the group consisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F,¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br; and pharmaceutically acceptable saltsthereof.
 18. The compound of claim 17, wherein: X is a bond or isselected from the group consisting of C₁₋₆alkylenyl, —C(O)—, —C(O)O— and—N(R¹⁰) C(O)—; R², R³, R⁴, R⁶, R⁷ and R⁸ are each independently hydrogenor are each independently selected from the group consisting ofC₁₋₃alkylNH—, halo, cyano, hydroxyl, —SR¹⁰—C(O)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy, C₆₋₁₄aryloxy,C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy, heteroarylC₂₋₅alkoxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; and R⁹ is hydrogenor is selected from the group consisting of halo, C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl,heteroaryl, halo-(CH₂CH₂)₁₋₆—; halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— and halo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—. 19.The compound of claim 17, wherein: X is a bond or is selected from thegroup consisting of C₁₋₆alkylenyl, —C(O)—, —C(O)O— and —N(R¹⁰) C(O)—;R², R⁴, R⁶ and R⁸ are each hydrogen; R³ and R⁷ are each independentlyselected from the group consisting of C₁₋₃alkylNH—, (C₁₋₃alkyl)₂N—,(halo-C₁₋₆alkyl)N(C₁₋₃alkyl)-, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆N(C₁₋₃alkyl)-,halo, hydroxyl, halo-C₁₋₆alkyl, C₆₋₁₀arylC₁₋₄alkyl,4-(halo-C₁₋₆alkyl)-triazol-1-yl)C₂₋₅alkoxy, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₅alkylNR¹⁰C(O)—,C₁₋₅alkylC(O)—; and R⁹ is hydrogen or is selected from the groupconsisting of halo, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, heteroaryl,halo-(CH₂CH₂)₁₋₆—; halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— and halo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—.
 20. Aradiolabeled compound of the formula III:

wherein: Y and Y′ are each independently a bond or are eachindependently selected from the group consisting of amino, halo, cyano,nitro, hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂, haloC₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy andheteroaryloxy when R¹¹ and R¹² are absent; R⁵, R⁶, R⁷ and R⁸ are eachindependently hydrogen or are each independently selected from the groupconsisting of amino, halo, cyano, nitro, hydroxyl, —SR¹⁰—C(O)NH₂,—C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—, C₃₋₆cycloalkoxy,C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy,C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—,(C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₅alkylNR¹⁰C(O)—,C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—, C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— andC₆₋₁₀arylC(O)O—; or at least one of R⁵ and R⁶, R⁶ and R⁷ or R⁷ and R⁸together with the carbon atoms to which they are attached to, form asubstituted or unsubstituted aromatic or non-aromatic carbocyclic orheterocyclic ring; provided that at least one of R⁵, R⁶, R⁷ and R⁸ is ahydrogen; each R¹⁰ is independently H or C₁₋₆alkyl; R¹¹ and R¹² are eachindependently absent, a hydrogen or are each independently selected fromthe group consisting of halo, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,halo-(CH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— and halo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—;provided that at least one of R⁵ to R¹² comprises a radiolabel; whereinthe radiolabel comprises a radionuclide selected from the groupconsisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I and ⁷⁷Br; andpharmaceutically acceptable salts thereof.
 21. The compound of claim 20,wherein: Y and Y′ are each independently selected from the groupconsisting of amino, halo, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂,halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₁₋₅alkoxy,H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O— and halo-CH₂CH₂O— when R¹¹ and R¹² areabsent; and R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or areeach independently selected from the group consisting of amino, halo,hydroxyl, —SR¹⁰, —C(O)NH₂, haloC₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl,C₃₋₆cycloalkyl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy,H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₂₋₅alkoxy,halo-C₂₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—, C₃₋₆cycloalkoxy,C₁₋₅alkylNR¹⁰—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₂₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-and halo-C₁₋₅alkylNR¹⁰C(O)—.
 22. The compound of claim 20, wherein: Yand Y′ are each independently a bond or are each independently selectedfrom the group consisting of amino, halo, hydroxyl, —C(O)NH₂,haloC₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆ alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O— and halo-CH₂CH₂O— when R¹¹ and R¹² areabsent; and R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or areeach independently selected from the group consisting ofhalo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—,FCH₂CH₂—(OCH₂CH₂)₁₋₆O—, haloC₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)- and halo-C₁₋₅alkylNR¹⁰C(O)—.
 23. Thecompound of claim 20, wherein: Y and Y′ are each independently a bond orare each independently selected from the group consisting of amino,halo, hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂, haloC₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-C₂₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—,C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy,C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy and heteroaryloxy when R¹¹ and R¹² areabsent; and R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen or areeach independently selected from the group consisting ofC₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy,C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—,(C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-, C₁₋₅alkylC(O)—, C₁₋₅alkylC(O)O—,C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—.
 24. A radiolabeled compound of theformula IV:

wherein: W is O or —N—X—R⁹; X is a bond or is selected from the groupconsisting of C₁₋₆alkylenyl, —C(O)—, —C(S)—, —C(O)O—, —C(S)O—,—N(R¹⁰)C(O)—, —N(R¹⁰)C(S)—, —S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—; Y and Y′ areeach independently a bond or are each independently selected from thegroup consisting of amino, halo, cyano, nitro, hydroxyl, —SR¹⁰,—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl,heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—,C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy,C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy and heteroaryloxy when R¹¹ and R¹² areabsent; or Y is

and R¹² is absent; R¹, R², R³ and R⁴ are each independently hydrogen orare each independently selected from the group consisting of amino,halo, cyano, nitro, hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl,perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy,heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy,C₁₋₅alkylNR¹⁰C(O)—, (C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-,halo-C₁₋₅alkylNR¹⁰C(O)—, C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—,C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— and C₆₋₁₀arylC(O)O—; or at least one ofR⁵ and R⁶, R⁶ and R⁷ or R⁷ and R⁸ together with the carbon atoms towhich they are attached to, form a substituted or unsubstituted aromaticor non-aromatic carbocyclic or heterocyclic ring; provided that at leastone of R¹, R², R³ and R⁴ is a hydrogen; R⁵, R⁶, R⁷, R⁸ and R^(o) areeach independently hydrogen or are each independently selected from thegroup consisting of amino, halo, cyano, nitro, hydroxyl, —SR¹⁰—C(O)NH₂,—C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—, C₃₋₆cycloalkoxy,C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy,C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—,(C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₅alkylNR¹⁰C(O)—,C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—, C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— andC₆₋₁₀arylC(O)O—; R⁹ is hydrogen or is selected from the group consistingof halo, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, halo-(CH₂CH₂)₁₋₆—;halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— andhalo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—; each R¹⁰ is independently H or C₁₋₆alkyl;and R¹¹ and R¹² are each independently absent, a hydrogen or are eachindependently selected from the group consisting of halo, C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl,heteroaryl, halo-(CH₂CH₂)₁₋₆—; halo-CH₂CH₂—(OCH₂CH₂)₁₋₆,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— and halo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—;provided that at least one of R¹ to R¹² comprises a radiolabel, asdefined herein; wherein the radiolabel comprises a radionuclide selectedfrom the group consisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹Iand ⁷⁷Br; and pharmaceutically acceptable salts thereof.
 25. Thecompound of claim 24, wherein: W is O or —N—X—R⁹; X is a bond or isselected from the group consisting of C₁₋₆alkylenyl, —C(O)—, —C(S)—,—C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—; and R¹, R², R³ and R⁴ are eachindependently hydrogen or are each independently selected from the groupconsisting of amino, halo, cyano, nitro, hydroxyl, —SR¹⁰, —C(O)NH₂,—C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—, C₃₋₆cycloalkoxy,C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy,C₆₋₁₀arylC₁₋₄alkoxy, C₁₋₅alkylC(O)—, C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— andC₆₋₁₀arylC(O)O—.
 26. The compound of claim 24, wherein: W is O or—N—X—R⁹; X is a bond or is selected from the group consisting ofC₁₋₆alkylenyl, —C(O)—, —C(O)O— and —N(R¹⁰)C(O)—; Y and Y′ are eachindependently a bond or are each independently selected from the groupconsisting of amino, halo, cyano, nitro, hydroxyl, —SR¹⁰—C(O)NH₂,—C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-CH₂CH₂O—, C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy and heteroaryloxy whenR¹¹ and R¹² are absent; and R¹, R², R³ and R⁴ are each independentlyhydrogen or are each independently selected from the group consisting ofamino, halo, hydroxyl, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, heteroaryl C₂₋₅alkoxy,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O— and C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—.
 27. Thecompound of claim 24, wherein: W is O; Y and Y′ are each independently abond or are each independently selected from the group consisting ofamino, halo, hydroxyl, —SR¹⁰—C(O)NH₂, halo-C₂₋₆alkyl, perhaloC₁₋₆alkyl,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄arylheteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—,C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy,C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy and heteroaryloxy when R¹¹ and R¹² areabsent; and R¹, R², R³ and R⁴ are each independently hydrogen or areeach independently selected from the group consisting ofhalo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-and halo-C₁₋₅alkylNR¹⁰C(O)—.
 28. The compound of claim 24, wherein: W isO; X is a bond or is selected from the group consisting ofC₁₋₆alkylenyl, —C(O)—, —C(O)O—; Y and Y′ are each independently a bondor are each independently selected from the group consisting of amino,halo, hydroxyl, —C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl,C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl,C₆₋₁₀arylC₁₋₄alkyl, heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—,C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—and halo-CH₂CH₂O— when R¹¹ and R¹² are absent; and R¹, R², R³ and R⁴ areeach independently hydrogen or are each independently selected from thegroup consisting of amino, halo, hydroxyl, —SR¹⁰, —C(O)NH₂, —C(S)NH₂,halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O— and halo-CH₂CH₂O—; or at least one of R¹and R², R² and R³ or R³ and R⁴ together with the carbon atoms to whichthey are attached to, form a substituted or unsubstituted aromatic ornon-aromatic carbocyclic or heterocyclic ring; provided that at leastany two of R¹, R², R³ and R⁴ are hydrogens; R⁹ is hydrogen or isselected from the group consisting of halo, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀-arylC₁₋₄alkyl, heteroaryl,halo-(CH₂CH₂)₁₋₆—; halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— and halo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—; andeach R¹⁰ is independently H or C₁₋₆alkyl.
 29. A radiolabel compound ofthe formula VI:

wherein: X is a bond or is selected from the group consisting ofC₁₋₆alkylenyl, —C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —N(R¹⁰)C(O)—,—N(R¹⁰)C(S)—, —S(O)N(R¹⁰)— and —N(R¹⁰)S(O)₂—; Y is a bond or is selectedfrom the group consisting of amino, halo, cyano, nitro, hydroxyl,—SR¹⁰—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl,heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—,C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy,C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy and heteroaryloxy; R⁵ and R⁶ are eachindependently hydrogen or are each independently selected from the groupconsisting of amino, halo, cyano, nitro, hydroxyl, —SR¹⁰, —C(O)NH₂,—C(S)NH₂, haloC₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—, C₃₋₆cycloalkoxy,C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy, C₆₋₁₄aryloxy,C₆₋₁₀-arylC₁₋₄alkoxy, heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—,(C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₅alkylNR¹⁰C(O)—,C₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—, C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)— andC₆₋₁₀arylC(O)O—; or R⁵ and R⁶ together with the carbon atoms to whichthey are attached to, form a substituted or unsubstituted aromatic ornon-aromatic carbocyclic or heterocyclic ring; R⁹ is hydrogen or isselected from the group consisting of halo, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,halo-(CH₂CH₂)₁₋₆—; halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— and halo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—; eachR¹⁰ is independently H or C₁₋₆alkyl; R¹¹ is a hydrogen or is selectedfrom the group consisting of halo, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,halo-(CH₂CH₂)₁₋₆—; halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— and halo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—;provided that at least one of R¹ to R¹¹ comprises a radiolabel, asdefined herein; wherein the radiolabel comprises a radionuclide selectedfrom the group consisting of ¹¹C, ¹³N, ¹⁵O, ¹⁸F, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹Iand ⁷⁷Br; and pharmaceutically acceptable salts thereof.
 30. Thecompound of claim 29, wherein: X is a bond or is selected from the groupconsisting of C₁₋₆alkylenyl, —C(O)—, —C(O)O—; Y is a bond or is selectedfrom the group consisting of amino, halo, —SR¹⁰—C(O)NH₂, —C(S)NH₂,haloC₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O— and halo-CH₂CH₂O—; R⁵ and R⁶ are eachindependently hydrogen or are each independently selected from the groupconsisting of amino, halo, hydroxyl, —SR¹⁰—C(O)NH₂, —C(S)NH₂,halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, heteroaryl,C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—, C₃₋₆cycloalkoxy,C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy, C₆₋₁₀aryloxy,C₆₋₁₀arylC₁₋₄alkoxy, heteroaryloxy, C₁₋₅alkylNR¹⁰C(O)—,(C₁₋₆alkyl)₂NC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-,halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-, halo-C₁₋₅alkylNR¹⁰C(O)—,CH₁₋₅alkylNR¹⁰C(O)O—, C₁₋₅alkylC(O)—, C₁₋₅alkylC(O)O—, C₆₋₁₀arylC(O)—and C₆₋₁₀arylC(O)O—; R⁹ is hydrogen or is selected from the groupconsisting of halo, C₁₋₆alkyl, C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl,C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl, halo-(CH₂CH₂)₁₋₆—;halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— andhalo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—; and R¹¹ is absent, a hydrogen or isselected from the group consisting of halo, C₁₋₆alkyl, C₃₋₆cycloalkyl,C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl,halo-(CH₂CH₂)₁₋₆—; halo-CH₂CH₂—(OCH₂CH₂)₁₋₆—,halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O(CO)— and halo-CH₂CH₂—(OCH₂CH₂)₁₋₆(CO)—; 31.The compound of claim 29, wherein: X is a bond or is selected from thegroup consisting of C₁₋₆alkylenyl, —C(O)—, —C(O)O—; Y is a bond or isselected from the group consisting of amino, halo, hydroxyl, —SR¹⁰,—C(O)NH₂, —C(S)NH₂, halo-C₁₋₆alkyl, perhaloC₁₋₆alkyl, C₁₋₆alkyl,C₃₋₆cycloalkyl, C₃₋₁₂cycloalkylC₁₋₅alkyl, C₆₋₁₄aryl, C₆₋₁₀arylC₁₋₄alkyl,heteroaryl, C₁₋₅alkoxy, H(OCH₂CH₂)₁₋₆O—, C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—,halo-C₁₋₅alkoxy, halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—,C₃₋₆cycloalkoxy, C₃₋₁₂cycloalkylC₁₋₅alkoxy, heteroarylC₂₋₅alkoxy,C₆₋₁₄aryloxy, C₆₋₁₀arylC₁₋₄alkoxy and heteroaryloxy when R¹¹ is absent;and R⁵ and R⁶ are each independently hydrogen or are each independentlyselected from the group consisting of halo-C₁₋₅alkoxy,halo-C₁₋₃alkyl(OCH₂CH₂)₁₋₆O—, halo-CH₂CH₂O—, halo-CH₂CH₂—(OCH₂CH₂)₁₋₆O—,halo-C₁₋₆alkylNR¹⁰C(O)CH(C₁₋₅alkyl)-, halo-C₁₋₆alkylOC(O)CH(C₁₋₅alkyl)-and halo-C₁₋₅alkylNR¹⁰C(O)—.
 32. A pharmaceutical composition for invivo imaging of amyloid deposits, comprising (a) a compound of claim 1and (b) a pharmaceutically acceptable carrier.
 33. A method ofdiagnosing Alzheimer's Disease or a predisposition thereto in a mammal,the method comprising: a) administering to the mammal a diagnosticallyeffective amount of a radiolabeled compound, wherein the compound passesthe blood-brain barrier and preferentially binds to a soluble ADoligomers, polymers and fibrils in a brain tissue and wherein thecompound is selected from the group consisting of radiolabeled flavones,coumarins, carbazoles, quinolinones, chromenones, imidazoles andtriazoles and their derivatives; b) allowing the compound to distributeinto the brain tissue; and c) imaging the brain tissue, wherein anincrease in binding of the compound to the brain tissue compared to anormal control level of binding indicates that the mammal is sufferingfrom or is at risk of developing Alzheimer's Disease.
 34. The method ofclaim 33, wherein the compound is a compound of claim
 1. 35. A method ofdiagnosing Alzheimer's Disease or a predisposition thereto in a mammal,the method comprising: a) administering to the mammal a diagnosticallyeffective amount of a radiolabeled compound or composition of claim 1,wherein the compound passes the blood-brain barrier and preferentiallybinds to a soluble AD oligomers, polymers and fibrils in a brain tissue;b) allowing the compound to distribute into the brain tissue; and c)imaging the brain tissue, wherein an increase in binding of the compoundto the brain tissue compared to a normal control level of bindingindicates that the mammal is suffering from or is at risk of developingAlzheimer's Disease.
 36. The method of claim 35, wherein theradiolabeled compound preferentially binds to fibrils.
 37. The method ofclaim 35, wherein the brain tissue comprises a frontotemporal region orthe hippocampal region.
 38. The method of claim 35, wherein the increasein binding is at least 10% greater than said normal control value. 39.The method of claim 33, wherein the compound is administered byintravenous injection.
 40. A method for detecting Alzheimer's Disease ora predisposition thereto in a living brain of a mammal, the methodcomprising: a) administering the mammal with a diagnostically effectiveamount of a radiolabeled compound that passes the blood-brain barrierand preferentially binds to a soluble AD oligomers, polymers and fibrilsin the brain, wherein the detectably-labeled compound is a compound ofclaim 1; b) allowing the compound to distribute into the brain tissue;and c) imaging the brain tissue, wherein an increase in binding of thecompound to the brain tissue compared to a normal control level ofbinding indicates that the mammal is suffering from or is at risk ofdeveloping Alzheimer's Disease.
 41. A method for detecting Alzheimer'sDisease or a predisposition thereto in a living brain of a mammal, themethod comprising: a) administering the mammal with a diagnosticallyeffective amount of a radiolabeled compound of claim 1, wherein thecompound passes the blood-brain barrier and preferentially binds to asoluble AD oligomers, polymers and fibrils in the brain; b) allowing thecompound to distribute into the brain tissue; and c) imaging the braintissue, wherein an increase in binding of the compound to the braintissue compared to a normal control level of binding indicates that themammal is suffering from or is at risk of developing Alzheimer'sDisease.
 42. A method of diagnosing Alzheimer's Disease or apredisposition thereto in a mammal, the method comprising: a)administering to the mammal a diagnostically effective amount of aradiolabeled compound, wherein the compound passes the blood-brainbarrier and preferentially binds to a soluble or insoluble AD oligomers,polymers, fibrils, hyperphosphorylated tau, neurofibrillary tangles,paired helical filaments and/or neurotoxic soluble oligomers in a brain,and wherein the radiolabeled compound is a compound of claim 1; and (b)employing a nuclear imaging technique selected from the group consistingof positron emission tomography (PET) and single photon emissioncomputed tomography (SPECT) for monitoring or visualizing a distributionof the radiolabeled compound within the brain or within a portionthereof.
 43. The method of claim 42 wherein the radiolabeled compound ora derivative thereof, is a compound of claim
 1. 44. A method fortreating a disease or condition, in a mammal in need thereof, selectedfrom the group consisting of anxiety, depression, schizophrenia,Alzheimer's Disease, stress-related disease, panic, a phobia, obsessivecompulsive disorder, obesity, post-traumatic stress syndrome, orepilepsy comprising administering to the mammal a therapeuticallyeffective amount of any one of claim
 1. 45. The method of claim 44,wherein the compound is a non-radiolabeled compound of claim
 1. 46. Themethod of claim 44, wherein the compound is administered rectally,topically, orally, sublingually or parenterally.
 47. The method of claim44, wherein the compound is administered from about 0.001 to about 100mg/kg of body weight of the mammal per day.
 48. The method of claim 44,wherein the compound is administered from about 0.1 to about 50 mg/kg ofbody weight of the mammal per day.